The DOI matches its Crossref record; 80 of the 85 references it cites were found in a registry or an index; none of the 60 sources its claims cite is checked for support yet.
Macrophage phenotypes during tissue repair
Open accessAbstract
Review on tissue repair and M1-like to M2a-like macrophages, exhibiting important differences from in vitro phenotypes. Mp are crucial for tissue repair and regeneration but can also contribute to tissue damage and fibrosis. Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best-characterized in vitro phenotypes are a proinflammatory “M1” phenotype, produced by exposure to IFN-γ and TNF-α, and an anti-inflammatory “M2a” phenotype, produced by IL-4 or IL-13. M2a Mp are frequently termed “wound healing” Mp, as they express factors that are important for tissue repair. This review will summarize current knowledge of Mp phenotypes during tissue repair and will argue that these in vivo Mp populations are heterogeneous and temporally regulated and do not conform to existing, in vitro-defined M1 or M2 phenotypes. Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a-associated characteristics. However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo. Additionally, M1- and M2-associated markers may be expressed simultaneously by actual tissue-repair Mp. Improved understanding of Mp phenotypes and their regulation may assist in generation of novel therapies based on manipulating Mp function to improve healing.
Overview
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Written from the paper’s full text.
TL;DR
This review argues that macrophages present during in vivo tissue repair are heterogeneous and temporally regulated and do not conform to the in vitro-defined M1 or M2a phenotypes. Early-repair macrophages are more proinflammatory than later ones, but neither population matches a discrete cultured phenotype.
Key findings
- M2a macrophages are widely termed "wound-healing" macrophages because IL-4/IL-13 treatment up-regulates TGF-β, arginase, and ECM components, but the review argues this nomination is "an oversimplification at best and likely not warranted."
- In a mouse sponge-implantation wound model, macrophages produced TGF-β despite no detectable IL-4 or IL-13 in wound fluids or cells and no Stat6 phosphorylation, indicating M2a activation is sufficient but not necessary for TGF-β production.
- M2a-associated markers are regulated independently in vivo: in murine subcutaneous wounds, CD206 increased with time, Ym1 was highest at 1 day and then decreased, and dectin-1 remained constant; CD206 expression was similar among TNF-α-high, -low, or -negative macrophages.
- iNOS expression by tissue-repair macrophages is context-dependent: highest at 1 day in mouse kidney ischemia-reperfusion, but only 10–15% of wound macrophages were iNOS-positive at peak in rat excisional skin wounds, and mouse muscle macrophages expressed iNOS after chemical injury but not after laceration.
- Human M2a macrophages or monocytes do not express arginase (unlike rodent), and human iNOS activity is much lower or absent (~20 nmol nitrite/10⁶ cells/24 h in rodent M1 macrophages; often undetectable in human).
Methods
- Narrative review summarizing current knowledge of macrophage phenotypes during tissue repair, drawing on cited in vitro and in vivo studies across skin, skeletal muscle, liver, kidney, and peritoneum.
- Compares in vitro-defined M1/M2a/b/c phenotypes with in vivo tissue-repair macrophage populations, including a summary table (Table 1) of activators, cytokines, iNOS, and markers (CD206, dectin-1, Ym1) across early and late repair.
- Includes some unpublished results from the authors' laboratory (mouse skeletal muscle laceration and chemical injury models).
Limitations
- Stated: many studies reporting M2a markers during repair did not verify that markers were expressed by macrophages rather than other cell types; whole-tissue cytokine content cannot determine macrophage phenotype; direct quantitative comparisons of cytokine production between cultured M1/M2a macrophages and in vivo tissue-repair macrophages are currently unavailable.
- Stated: rodent and human macrophages do not exhibit entirely similar responses to in vitro activation, and whether species-dependent differences exist in in vivo repair is undetermined.
- Evident from the text: several key supporting observations are unpublished results from the authors' own laboratory, and the review notes that the factors regulating in vivo macrophage phenotype "remain to be elucidated."
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Claims the paper makes
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Mp can adopt a variety of functional phenotypes in response to different stimuli; two of the best-characterized in vitro phenotypes are a proinflammatory”
§ Macrophage phenotypes during tissue repair > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Mp, in particular, are known to be essential to regeneration, repair, and remodeling in numerous tissues [1][2][3][4][5].”
§ Macrophage phenotypes during tissue repair > Introduction
What the sources say
- Not checked yetcites [1][2][3][4][5]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“However, chronic inflammation and persistent Mp accumulation are often associated with tissue destruction and fibrosis [6 -8].”
§ Macrophage phenotypes during tissue repair > Introduction
What the sources say
- Not checked yetcites [6] Moreira, 2011, Macrophages in allergic asthma: fine-tuning their pro- and anti-inflammatory actions for disease resolution, J. Interfron Cytokine Res. source
- Not checked yetcites [7] Moyer, 2011, Regeneration versus fibrosis in skeletal muscle, Curr. Opin. Rheumatol. source
- Not checked yetcites [8] Murray, 2011, Protective and pathogenic functions of macrophage subsets, Nat. Rev. Immunol. source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesNone of the sources cited for this claim have been checked yet.
In the paper
“The M1-associated cytokines IL-1, TNF-␣, IL-6, and IL-12 are expressed by Mp during the first few hours to days after acute injury in numerous tissues, including skin [33,60,61], liver [62], kidney [63], and skeletal muscle [57,64].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [33] Daley, 2010, The phenotype of murine wound macrophages, J. Leukoc. Biol. source
- Not checked yetcites [60] Mirza, 2011, Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice, Cytokine source
- Not checked yetcites [61] Sindrilaru, 2011, An unrestrained pro-inflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice, J. Clin. Invest. source
- Not checked yetcites [62] Karlmark, 2010, The fractalkine receptor CX3CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes, Hepatology source
- Not checked yetcites [63] Lee, 2011, Distinct macrophage phenotypes contribute to kidney injury and repair, J. Am. Soc. Nephrol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Thus, available evidence indicates that M1 and M2a/b/c are not discrete Mp differentiation states but instead represent convenient but limited and arbitrary in vitro-defined reference points on a time-dependent and multidimensional continuum of possible Mp phenotypes and functions [9].”
§ Macrophage phenotypes during tissue repair > EVOLVING Mp ACTIVATION PARADIGMS
What the sources say
- Not checked yetcites [9] Mosser, 2008, Exploring the full spectrum of macrophage activation, Nat. Rev. Immunol. source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, the presence of arginase or even of arginase-expressing Mp does not necessarily imply that IL-4/IL-13-induced M2a Mp are present in a tissue.”
§ Macrophage phenotypes during tissue repair > EVIDENCE FOR M2a Mp AS TISSUE-REPAIR Mp
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In the paper
“Importantly, in contrast to rodent Mp, human M2a Mp or monocytes do not express arginase [36,37].”
§ Macrophage phenotypes during tissue repair > EVIDENCE FOR M2a Mp AS TISSUE-REPAIR Mp
What the sources say
- Not checked yetcites [36] Munder, 2005, Arginase I is constitutively expressed in human granulocytes and participates in fungicidal activity, Blood source
- Not checked yetcites [37] Raes, 2005, Macrophage galactose-type C-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation, J. Leukoc. Biol. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This review will address recent advances in our understanding of Mp phenotypes during tissue repair and will argue that the Mp populations that participate in tissue repair are not analogous to in vitro M2a Mp.”
§ Macrophage phenotypes during tissue repair > Introduction
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, phenotypic markers that appear to be coregulated in cultured Mp can be expressed independently of each other in vivo.”
§ Macrophage phenotypes during tissue repair > Abstract
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes? Based: unclearA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mp during the early stages of tissue repair exhibit a more proinflammatory phenotype than their later counterparts, which in turn may exhibit some M2a-associated characteristics.”
§ Macrophage phenotypes during tissue repair > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The phases of tissue repair (inflammation, proliferation, remodeling) are universal across tissues.
- Probably not a substantial claim. 5
- It may state two separate claims as one. 24
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, after mouse skeletal muscle laceration, Mp expression of TGF- mRNA and IL-10 mRNA appears to peak early, ϳ3 days postinjury (unpublished results).”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Studies from our own laboratory have produced contradictory data in two different mouse muscle injury models: skeletal muscle Mp express iNOS mRNA at 5 days after chemically induced injury [57] but do not express iNOS at any time-point after laceration injury (unpublished results).”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [57] Cheng, 2008, Endogenous interferon-γ is required for efficient skeletal muscle regeneration, Am. J. Physiol. Cell. Physiol. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“For instance, in a mouse wound-healing model, Mp expression of the M2a marker CD206 does not require IL-4 or IL-13 and does not correlate, negatively or otherwise, with TNF-␣ production [33].”
§ Macrophage phenotypes during tissue repair > EVIDENCE FOR M2a Mp AS TISSUE-REPAIR Mp
What the sources say
- Not checked yetcites [33] Daley, 2010, The phenotype of murine wound macrophages, J. Leukoc. Biol. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“two of the best-characterized in vitro phenotypes are a proinflammatory”
§ Macrophage phenotypes during tissue repair > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“M2a Mp are frequently termed”
§ Macrophage phenotypes during tissue repair > Abstract
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“The M1 activator IFN-␥ is up-regulated rapidly after injury to skeletal muscle and skin and is required for proper healing of these tissues [55][56][57][58].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [55][56][57][58]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, whereas it is clear that treatment of cultured Mp with particular cytokines produces characteristic phenotypes, the presence of one or a few phenotypic markers in vivo does not demonstrate that the Mp was activated by the associated cytokine or that other aspects of the phenotype induced by that cytokine will also be present.”
§ Macrophage phenotypes during tissue repair > EVIDENCE FOR M2a Mp AS TISSUE-REPAIR Mp
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Wound healing is thus not a single, well-defined function of Mp but comprises its own spectrum of overlapping functions, including phagocytosis, secretion of cytokines and growth factors, as well as matrix remodeling, all of which may be performed by Mp of different phenotypes.”
§ Macrophage phenotypes during tissue repair > EVOLVING Mp ACTIVATION PARADIGMS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In numerous physiological and pathological states, Mp exhibit extensive heterogeneity and plasticity, and tissue repair is no exception.”
§ Macrophage phenotypes during tissue repair > Introduction
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, existing data on anti-inflammatory cytokine production suggest that Mp may become more M2a-like as repair progresses, although this transition may not happen in all situations.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The phases of tissue repair (inflammation, proliferation, remodeling) are universal across tissues.
In the paper
“In contrast, in a mouse sponge-implantation model of skin wounding, deletion of IL-4R␣ has no effect on Mp phenotype, and IL-4 and IL-13 are not detected in wound cells or fluids at any time, indicating that despite their predominantly anti-inflammatory cytokine profile, these cells are not bona fide M2a Mp [33].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [33] Daley, 2010, The phenotype of murine wound macrophages, J. Leukoc. Biol. source
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, during mouse skin wound healing, Mp expression of TGF- mRNA and protein increases over the first 7-10 days postinjury, whereas proinflammatory cytokine production decreases [33,60], consistent with the expression of an M2a-like phenotype during the later stages of repair.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Similarly, after peritoneal incisional wounding, peritoneal exudate cells transiently express elevated Ym1 and FIZZ1 mRNA, although this cell population contains lymphocytes and neutrophils in addition to Mp [70], and each of these cell types could express one or both genes [76,77].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [70] Loke, 2007, Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection, J. Immunol. source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Seven days after photochemical injury to the liver, CD206ϩ cells are observed near the border of the injured site [68], although these cells were not verified specifically as Mp, and no other time-points were examined.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [68] Kawao, 2011, Urokinase-type plasminogen activator contributes to heterogeneity of macrophages at the border of damaged site during liver repair in mice, Thromb. Haemost. source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Collectively, data from these studies indicate that the M2a markers CD206, Ym1, and dectin-1 can be regulated independently of each other in skin-wound Mp and can be coexpressed with M1-associated or proinflammatory genes and proteins.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“In murine skeletal muscle, however, Mp expression of TGF- and IL-10 mRNA increases over the first few days after toxin-induced injury, peaks during the intermediate stages of healing, and then declines sharply, despite continued presence of Mp within the healing muscle [65].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [65] Perdiguero, 2011, p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair, J. Cell Biol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Thus, Mp during skin wound healing exhibit a heterogeneous and temporally regulated phenotype that does not conform strictly to M1/M2 categorization [33].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [33] Daley, 2010, The phenotype of murine wound macrophages, J. Leukoc. Biol. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Tissue repair in mice is representative of tissue repair in humans.
- Rests on an assumption: The phases of tissue repair (inflammation, proliferation, remodeling) are universal across tissues.
In the paper
“However, although CD206, Ym1, and dectin-1 are expressed by murine subcutaneous wound Mp at 1, 3, and 7 days postinjury [33], these three M2a-associated proteins exhibit entirely different temporal patterns: CD206 increases somewhat with time, whereas Ym1 is expressed most highly at 1-day postinjury and then decreases, and dectin-1 expression remains constant [33].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [33] Daley, 2010, The phenotype of murine wound macrophages, J. Leukoc. Biol. source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Numerous studies in other tissues have reported that M2a markers are present during tissue repair, but many of these studies have not determined whether these markers are expressed by Mp or by other cell types, and any conclusions drawn regarding Mp phenotype are therefore dubious.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In addition to proinflammatory cytokine production, robust expression of iNOS is a hallmark of M1 activation in rodent Mp [14], although iNOS activity in human Mp appears to be much lower or absent entirely (ϳ20 nmol nitrite/10 6 cells/24 h in rodent M1 Mp; often undetectable in human Mp) [66].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Additionally, as IL-4/-13 activation is not always required for up-regulation of IL-10 and TGF- [33], the presence of other aspects of the M2a phenotype should not be inferred from cytokine expression alone.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [33] Daley, 2010, The phenotype of murine wound macrophages, J. Leukoc. Biol. source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, IL-4 gene expression is elevated from 1 to 7 days in rat skin wounds [56], and protein expression is elevated between 12 h and 10 days in human skin wounds (peak ϳ12 pg/mg protein in injured skin vs. nearly undetectable in uninjured) [58]; IL-4 protein is present at similar levels in infarcted rat myocardium [72].”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
What the sources say
- Not checked yetcites [56] Miao, 2012, Diabetes-impaired wound healing and altered macrophage activation: a possible pathophysiologic correlation, Wound Repair Regen. source
- Not checked yetcites [58] Takamiya, 2008, Simultaneous detection of eight cytokines in human dermal wounds with a multiplex bead-based immunoassay for wound age estimation, Int. J. Legal Med. source
- Not checked yetcites [72] Fraccarollo, 2008, Immediate mineralocorticoid receptor blockade improves myocardial infarct healing by modulation of the inflammatory response, Hypertension source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In short, tissuerepair Mp exhibit complex and heterogeneous phenotypes that change throughout the repair process and do not correspond to existing, in vitro -defined categories.”
§ Macrophage phenotypes during tissue repair > CONCLUDING REMARKS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Whereas Mp are known to promote tissue-repair functions such as wound debridement, cell proliferation, angiogenesis, and matrix remodeling, much remains to be learned about the mechanisms by which Mp accomplish these functions.”
§ Macrophage phenotypes during tissue repair > CONCLUDING REMARKS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✗ Based: failsProbably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A proinflammatory-to-anti-inflammatory transition may indeed occur in many situations, although this appears to be context-dependent”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas Mp during the early stages of tissue repair seem to present a more generally proinflammatory profile than their later counterparts, early Mp may lack iNOS expression or may express CD206, Ym1, and IL-10 in addition to proinflammatory cytokines, indicating that these early-repair Mp do not exhibit an entirely M1 phenotype.”
§ Macrophage phenotypes during tissue repair > CONCLUDING REMARKS
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Given the growing belief that M2a Mp participate in tissue repair, surprisingly few studies have actually examined Mp-specific expression of M2a-associated genes or proteins in vivo or performed quantitative comparisons of cytokine production by cultured M1/M2a Mp versus in vivo tissuerepair Mp.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Similarly, whereas many potential modulators of Mp activation have been identified in vitro, the actual factors that regulate Mp phenotype during tissue repair remain to be elucidated.”
§ Macrophage phenotypes during tissue repair > CONCLUDING REMARKS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Tissue repair in mice is representative of tissue repair in humans.
“In mouse and human skin wounds and in injured mouse kidney, Mp expression of CD206 increases during the later stages of repair [33,60,61,63].”
The paper relies on this without support.
The phases of tissue repair (inflammation, proliferation, remodeling) are universal across tissues.
“Across diverse tissues, repair after injury occurs in overlapping phases of inflammation, proliferation, and remodeling.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The classical model distinguishes two major polarization phenotypes, which represent a continuum, providing a balance between the pro‐ and anti‐inflammatory responses by alternating between classically (M1) or alternatively (M2) activated macrophages.[ 37 , 38 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [37]
Experimental — accuracy not yet measuredIn the citing paper
“Recent studies have shown that Mp phenotypes change over the different phases of tissue repair and that the sequential appearance of these phenotypes may be required for efficient repair (11,14,29,49,50).”
From Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice (2014) · cites this paper as [50]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Table says the IL-10 time course is unknown despite describing it in muscle
MinorTable 1 says the IL-10 time course is not known, but the text describes a rise, intermediate peak, and subsequent decline in macrophage IL-10 mRNA after toxin-induced skeletal muscle injury. If the table means only skin wounds, it does not say so.
“TGF- increases with time (skin); IL-10 time course not known.”
“In murine skeletal muscle, however, Mp expression of TGF- and IL-10 mRNA increases over the first few days after toxin-induced injury, peaks during the intermediate stages of healing, and then declines sharply, despite continued presence of Mp within the healing muscle [65].”
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“CHR pretreatment increased mRNA expression levels of AAM markers, Il10, Arg1, Fizz1, and Ym1, and the release of IL-10 and Arginase activity (Figures 6A,B).”
BackgroundInfluentialTargeting Macrophage Polarization for Reinstating Homeostasis following Tissue Damage
Du, Q., Dickinson, A., Nakuleswaran, P., Maghami, S., Alagoda, S., Hook, A. L., & Ghaemmaghami, A. M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137278 · Cited by 52
“M1 macrophages mainly secrete pro-inflammatory molecules to eliminate invading pathogens and boost inflammation, while M2 macrophages express various anti-inflammatory molecules that support tissue regeneration and remodeling [7,11,12].”
BackgroundInfluentialLiu, L., Yue, Y., & Xiong, S. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.07.021 · Cited by 46
“Cytokines IFN-γ and IL-4/IL-13 have been reported to be crucial for M1 and M2a polarization, respectively [39].”
BackgroundTrypsin, Tryptase, and Thrombin Polarize Macrophages towards a Pro-Fibrotic M2a Phenotype
White, M. J. V., & Gomer, R. H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0138748 · Cited by 48
“M2 macrophages are associated with decreased inflammation and increased tissue repair [26, 30].”
BackgroundAberrant Wound Healing in an Epidermal Interleukin-4 Transgenic Mouse Model of Atopic Dermatitis
Zhao, Y. H., Bao, L., Chan, L. S., DiPietro, L. A., & Chen, L. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146451 · Cited by 47
“In the process of tissue repair, M1 dominates the macrophage population in the inflammatory phase while M2dominates in the later stages of proliferation and remodeling [43].”
BackgroundRegeneration and repair of human digits and limbs: fact and fiction
Shieh, S., & Cheng, T. (2015) · Regeneration · doi:10.1002/reg2.41 · Cited by 45
“M1 phenotype macrophages respond to in- flammatory and antimicrobial events, and M2 phenotype macrophages potently have an important anti-inflammatory role in wound healing (Mosser & Edwards 2008; Murray & Wynn 2011; Novak & Koh 2013).”
BackgroundThe renal microenvironment modifies dendritic cell phenotype
Chessa, F., Mathow, D., Wang, S., Hielscher, T., Atzberger, A., Porubský, Š., Gretz, N., Burgdorf, S., Gröne, H., & Popović, Z. V. (2015) · Kidney International · doi:10.1038/ki.2015.292 · Cited by 46
A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice
Ghebremedhin, A., Salam, A. B., Adu-Addai, B., Noonan, S., Stratton, R. J., Ahmed, M. S. U., Khantwal, C. M., Martin, G. R., Lin, H., Andrews, C., et al. (2023) · Cells · doi:10.3390/cells12091254 · Cited by 65
“Several studies have demonstrated that activated CD206-positive M2 macrophages in fibrotic lesions produce high amounts of IL-10, IL-6, TNF-α, and TGFβ1 that enhance collagen synthesis and deposition [15,23].”
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Vitamin D Receptor–Dependent Signaling Protects Mice From Dextran Sulfate Sodium-Induced Colitis
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Immune tuning scaffold for the local induction of a pro-regenerative environment
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Modulating effect of low intensity pulsed ultrasound on the phenotype of inflammatory cells.
da Silva, E. M., Mesquita-Ferrari, R., França, C., Andreo, L., Bussadori, S., & Fernandes, K. (2017) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2017.11.108 · Cited by 46
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“Activation of M2b is mainly mediated by immune complexes and Toll-like receptors, secreting IL10, inhibiting acute inflammatory responses caused by bacterial endotoxin, and promoting Th2 immune response; M2c is induced by IL-10 and glucocorticoids, secreting IL-10 and TGF-β1 mainly play a role in regulating and inhibi…”
BackgroundLi, B., Liu, C., Tang, K., Dong, X., Xue, L., Su, G., Zhang, W., & Jin, Y. (2019) · Inflammation Research · doi:10.1007/s00011-019-01285-1 · Cited by 44
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“Using in vitro and in vivo testing, the authors demonstrate immunomodulatory behavior of the Chitosan-FPHS—reducing M1 marker protein iNOS by 60% and increasing M2 marker proteins Arg-1 and Ym1/2 by 330% [213].”
BackgroundInfluentialThe Vitamin D Receptor Regulates Tissue Resident Macrophage Response to Injury.
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Fungal Recognition and Host Defense Mechanisms
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Patchouli Essential Oil and Its Derived Compounds Revealed Prebiotic-Like Effects in C57BL/6J Mice
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“Evidence included the shifting the pro-inflammatory M1 macrophages to the antiinflammatory M2 macrophages based on the expressions of M1 biomarkers (iNOS and CXCL 10) and M2 macrophage biomarkers (arginase 1) (Luzina et al., 2012; Novak and Koh, 2013; Kühl et al., 2015).”
BackgroundA practical guide for evaluating the osteoimmunomodulatory properties of biomaterials
Mestres, G., Carter, S. D., Hailer, N. P., & Díez-Escudero, A. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.05.038 · Cited by 42
“Generally, they are classified as M2a, stimulating fibroblast and extra-cellular matrix formation (ECM) [34 , 35] ; M2b, responsible for balancing the inflammatory process [36] ; M2c, responsible for matrix renovation and vascularization [37 , 38] ; and M2d, important pro-angiogenic modulators [39] .”
BackgroundLabel-free macrophage phenotype classification using machine learning methods
Hourani, T., Perez‐Gonzalez, A., Khoshmanesh, K., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-32158-7 · Cited by 41
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“Inflammatory factors are downregulated in M2 macrophages, whereas anti-inflammatory cytokine IL-10, transforming growth factor-b (TGF-b) or angiogenic factor vascular endothelial growth factor (VEGF), as well as the M2markers Arginase-1 and Ym1 are upregulated in different types of M2 macrophages (Ferrante and Leibovi…”
BackgroundInfluentialEscobar, G., Escobar, A. F., Ascui, G., Tempio, F., Ortiz, M. C., Pérez, C., & López, M. N. (2018) · Regenerative Medicine · doi:10.2217/rme-2017-0122 · Cited by 41
“Macrophages are immune cells that also participate of tissue repair and remodeling [17,18].”
Backgroundde Sousa, J. R., Vasconcelos, P. F. D. C., & Quaresma, J. A. S. (2019) · Infection and Drug Resistance · doi:10.2147/idr.s208576 · Cited by 48
“However, current evidence further strengthens their relationship with components of the innate and adaptive immune systems.(115,116)”
BackgroundThe promise and challenges of cell therapy for psoriasis*
Lwin, S. M., Snowden, J. A., & Griffiths, C. E. M. (2021) · British Journal of Dermatology · doi:10.1111/bjd.20517 · Cited by 42
Current Biological Strategies to Enhance Surgical Treatment for Rotator Cuff Repair
Zhang, C., Wu, J., Li, X., Wang, Z., Lu, W. W., & Wong, T.-M. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.657584 · Cited by 42
“, 2019), because studies have shown that M2 macrophagederived exosomes contain many important proteins and miRNA that stimulate the healing process of rotator cuff (Novak and Koh, 2013; Chamberlain et al., 2019).”
BackgroundA novel phosphodiesterase 4 inhibitor, AA6216, reduces macrophage activity and fibrosis in the lung
Matsuhira, T., Nishiyama, O., Tabata, Y., Kaji, C., Kubota-Ishida, N., Chiba, Y., Sano, H., Iwanaga, T., & Tohda, Y. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173508 · Cited by 41
Macrophages as Effectors of Acute and Chronic Allograft Injury
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Zamani, R., Pilehvar‐Soltanahmadi, Y., Alizadeh, E., & Zarghami, N. (2017) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2017.1367689 · Cited by 41
“On the other hand, in the late inflammatory stage, the process of efferocytosis (eliminating apoptotic cells) and the alteration in wound microenvironment drive the M1 macrophages toward M2 polarization with high production of antiinflammatory cytokines IL-4, IL-10, and TGF-b [5].”
Neutrophils in Biomaterial-Guided Tissue Regeneration: Matrix Reprogramming for Angiogenesis
Fetz, A. E., Radic, M. Z., & Bowlin, G. L. (2020) · Tissue Engineering Part B Reviews · doi:10.1089/ten.teb.2020.0028 · Cited by 40
“96 Initially upregulating MMP-9 secretion from abundant proangiogenic N2 neutrophils, followed by their timely removal from the wound site to encourage resolution, may stimulate matrix reprogramming.”
Battiston, K. G., Labow, R. S., Simmons, C. A., & Santerre, J. P. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2015.05.038 · Cited by 38
The role of Kupffer cells in the hepatic response to silver nanoparticles
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Ferreira, D. W., Ulecia-Morón, C., Alvarado-Vazquez, P. A., Cunnane, K., Moracho-Vilrriales, C., Grosick, R. L., Cunha, T. M., & Romero-Sandoval, E. A. (2019) · Immunobiology · doi:10.1016/j.imbio.2019.10.011 · Cited by 40
Male Macrophages and Fibroblasts from C57/BL6J Mice Are More Susceptible to Inflammatory Stimuli
Barcena, M. L., Niehues, M. H., Christiansen, C., Estepa, M., Haritonow, N., Sadighi, A. H., Müller‐Werdan, U., Ladilov, Y. V., & Regitz‐Zagrosek, V. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.758767 · Cited by 36
“The M2 marker RELM-a was also markedly upregulated in both male and female macrophages after IL-4/IL-13 co-treatment ( Figure 4C ).”
InfluentialKim, Y., Oreffo, R. O. C., & Dawson, J. I. (2022) · Bone · doi:10.1016/j.bone.2022.116389 · Cited by 38
“Although these subtypes all describe anti-inflammatory properties, M2a and M2b designate immunoregulatory effects, whereas M2c is associated with immunosuppressive phenotypes and the anabolic phase of extracellular matrix (ECM) remodelling [26,27].”
Circadian modulation of microglial physiological processes and immune responses
Guzmán‐Ruiz, M. A., Guerrero‐Vargas, N. N., Lagunes‐Cruz, A., González‐González, S., García‐Aviles, J. E., Hurtado‐Alvarado, G., Méndez‐Hernández, R., Chavarría, A., Morin, J., Arriaga-Ávila, V. S., et al. (2022) · Glia · doi:10.1002/glia.24261 · Cited by 37
“…1β, IL-12) (Gordon & Taylor, 2005; Villalta et al., 2009),and an “alternative” antiinflammatory (M2) state that expresses arginase 1 (ARG1), antiinflammatory cytokines (Il4, Il10, Il13, and TGF-β), CD206, among others (Colton, 2009; Novak & Koh, 2013; Shechter & Schwartz, 2013; Stein et al., 1992).”
Research Progress on Biomaterials with Immunomodulatory Effects in Bone Regeneration
Li, J., Qu, Y., Chu, B., Wu, T., Pan, M., Mo, D., Li, L., Ming, Y., Yang, Y. S., Wang, M., et al. (2025) · Advanced Science · doi:10.1002/advs.202501209 · Cited by 50
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“Although the mechanism of this e ff ect was not directly identified, we found that early reperfusion increased the number of anti-inflammatory CD206 + M2 macrophage / microglia, which are associated with tissue repair [29–31].”
Karnam, K. C., Sedmaki, K., Sharma, P., Mahale, A. B., Ghosh, B., & Kulkarni, O. P. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121574 · Cited by 35
Locally Produced IL-10 Limits Cutaneous Vaccinia Virus Spread
Cush, S. S., Reynoso, G. V., Kamenyeva, O., Bennink, J. R., Yewdell, J. W., & Hickman, H. D. (2016) · PLoS Pathogens · doi:10.1371/journal.ppat.1005493 · Cited by 35
“M2-polarized (also known as "alternatively activated" or "wound healing") macrophages promote tissue restoration post-trauma, infection, or allergic inflammation [45] [46] [47] [48] .”
BackgroundFujisaka, S., Usui, I., Nawaz, A., Takikawa, A., Kado, T., Igarashi, Y., & Tobe, K. (2016) · Diabetology International · doi:10.1007/s13340-016-0290-y · Cited by 39
Wang, L., Hussain, Z., Zheng, P., Zhang, Y., Cao, Y., Gao, T., Zhang, Z., Zhang, Y., & Pei, R. (2023) · Journal of Materials Chemistry B · doi:10.1039/d2tb02403a · Cited by 36
Gamma Delta T Cells Regulate Wound Myeloid CELL Activity After Burn
Rani, M., Zhang, Q., & Schwacha, M. G. (2014) · Shock · doi:10.1097/shk.0000000000000176 · Cited by 36
Grabarz, F., de Aguiar, C. F., Corrêa-Costa, M., Braga, T. T., Hiyane, M. I., Andrade‐Oliveira, V., Landgraf, M. A., & Câmara, N. O. S. (2017) · Inflammopharmacology · doi:10.1007/s10787-017-0383-7 · Cited by 35
“The deletion of IL-4 receptor a-chain significantly decreased the expression of M2 markers such as FIZZ-1 and arginase-1 reinforcing the correlation between the Th2 cytokines and the M2 phenotype (Novak and Koh 2013).”
BackgroundVarela, P., Sartori, S., Viebahn, R., Salber, J., & Ciardelli, G. (2019) · Journal of Applied Biomaterials & Functional Materials · doi:10.1177/2280800019830355 · Cited by 35
Hydroxyapatite Use in Spine Surgery—Molecular and Clinical Aspect
Litak, J., Czyżewski, W., Szymoniuk, M., Pastuszak, B., Litak, J., Grzegorz Litak, A., Grochowski, C., Rahnama, M., & Kamieniak, P. (2022) · Materials · doi:10.3390/ma15082906 · Cited by 35
“There are two classic phenotypes of macrophages, which include either pro-inflammatory M1 and pro-healing (anti-inflammatory) M2 polarization, with the latter being responsible for tissue repair enhancement [51,52].”
BackgroundNoushin, T., Hossain, N. I., & Tabassum, S. (2022) · Frontiers in Nanotechnology · doi:10.3389/fnano.2022.851041 · Cited by 38
Pervin, M., Karim, M. R., Kuramochi, M., Izawa, T., Kuwamura, M., & Yamate, J. (2018) · Toxicologic Pathology · doi:10.1177/0192623318776898 · Cited by 33
Function of Connexin-43 in Macrophages
Rodjakovic, D., Salm, L., & Beldi, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031412 · Cited by 34
“• M2 macrophages possess stronger migratory ability compared to M1 macrophages, have increased phagocytic properties and are in general anti-inflammatory and considered to help tissue repair [62, 63].”
BackgroundWnt Signaling in the Phenotype and Function of Tumor-Associated Macrophages
Tigue, M. L., Loberg, M. A., Goettel, J. A., Weiss, W. A., Lee, E. N., & Weiss, V. L. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-1403 · Cited by 40
Role of renal tubular epithelial cells and macrophages in cisplatin-induced acute renal injury
Gao, J., Deng, Q., Yu, J. Q., Wang, C., & Wei, W. (2024) · Life Sciences · doi:10.1016/j.lfs.2024.122450 · Cited by 41
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Fibroblasts Control Macrophage Differentiation during Pulp Inflammation
Fournis, C. L., Jeanneau, C., Giraud, T., et al. (2021) · Journal of Endodontics · doi:10.1016/j.joen.2021.06.015 · Cited by 33
Investigational drugs in clinical trials for macular degeneration
Tolentino, M. J., & Tolentino, A. J. (2022) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2022.2113375 · Cited by 34
Long, J., Qin, Z., Chen, G., Song, B., & Zhang, Z. (2022) · Biomaterials Science · doi:10.1039/d2bm01204a · Cited by 36
Dahri, M., Rezaeian, M., Sadeghzadeh, H., Beheshtizadeh, N., Sadeghi, M. M., Zakerhamidi, D., Faraji, S. N., Pakdel, H., Dahri, B., Maleki, R., et al. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118360 · Cited by 37
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“Macrophages, which are involved in all stages of wound healing, promote inflammation in the early stages and regulate the process of wound repair by activating the proliferation of fibroblasts, keratinocytes, and endothelial cells.(21,22) Alternatively, studies have shown that macrophage depletion during the prolifera…”
BackgroundSuess, P. M., Chinea, L. E., Pilling, D., & Gomer, R. H. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801559 · Cited by 28
“In addition to fibrocytes, macrophages potentiate wound healing (40, 41), and factors released from platelets, such as IL-1, MIP-1a, CCL5, and TGF-b, affect macrophage recruitment, adhesion, activity, and cytokine release (42, 43).”
BackgroundMacrophage and osteoclast polarization in bisphosphonate associated necrosis and osteoradionecrosis
Wehrhan, F., Möbius, P., Amann, K., Ries, J., Preidl, R. H. M., Neukam, F. W., & Weber, M. (2017) · Journal of Cranio-Maxillofacial Surgery · doi:10.1016/j.jcms.2017.02.023 · Cited by 33
“M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT Wehrhan F et al. 12 During wound healing, a shift of macrophage polarization initially towards M1 for clearance of pathogens and afterwards towards regenerative M2 macrophages occurs (Mantovani et al., 2013, Novak and Koh, 2013).”
BackgroundWang, Y., Qi, H., Miron, R. J., & Zhang, Y. (2019) · Clinical Implant Dentistry and Related Research · doi:10.1111/cid.12819 · Cited by 32
Nadella, V., Garg, M., Kapoor, S., Barwal, T. S., Jain, A., & Prakash, H. (2020) · Annals of Translational Medicine · doi:10.21037/atm-20-695 · Cited by 31
“On the other hand, Th2 cytokines such as IL-4, IL-10, IL-13 tune macrophages towards M2-like phenotype that display anti-inflammatory responses such as tissue repair and wound healing (12).”
BackgroundThe retinal pigment epithelium as a gateway for monocyte trafficking into the eye
Benhar, I., Reemst, K., Kalchenko, V., & Schwartz, M. (2016) · The EMBO Journal · doi:10.15252/embj.201694202 · Cited by 31
“Notably, the expression of both pro-and anti-inflammatory cytokines by these cells highlights their heterogeneity and reflects their ability to respond to and affect the immunological milieu in the eye to best support repair (Mosser & Edwards, 2008; Sica & Mantovani, 2012; Novak & Koh, 2013).”
Won, J., Kim, W. J., Shim, J. S., & Ryu, J. (2022) · Macromolecular Bioscience · doi:10.1002/mabi.202200162 · Cited by 30
Sun, M., Li, Y., Xu, G., Zhu, J., Lu, R., An, S. L., Zeng, Z., Deng, Z., Cheng, R., Zhang, Q., et al. (2024) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0322 · Cited by 30
Application of Biomaterials in Diabetic Wound Healing: The Recent Advances and Pathological Aspects
Han, C., Singla, R. K., & Wang, C. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17101295 · Cited by 40
“M2 macrophages have four subtypes [51]: M2a which promotes cell proliferation and ECM production [52], M2b which inhibits inflammation [53], M2c has matrix remodeling capacity [54], while M2d has angiogenic and remodeling activity [55].”
Is Metrnl an Adipokine İnvolved in the Anti-inflammatory Response to Acute Exacerbations of COPD?
Kerget, B., Afşin, D. E., Kerget, F., Aşkın, S., & Akgün, M. (2020) · Lung · doi:10.1007/s00408-020-00327-4 · Cited by 29
A Population of Injury-Responsive Lymphoid Cells Expresses mpeg1.1 in the Adult Zebrafish Heart
Moyse, B., & Richardson, R. J. (2020) · ImmunoHorizons · doi:10.4049/immunohorizons.2000063 · Cited by 30
“In humans and rodents, in which MNP lineages are routinely defined by Ab labeling of precise protein markers, the diverse and crucial roles that monocyte and macrophage subpopulations play during repair and regeneration of the heart and other tissues has begun to be characterized (5, 16, 17).”
BackgroundPadma, A. M., Alshaikh, A. B., Song, M. J., Akouri, R., Oltean, M., Brännström, M., & Hellström, M. (2021) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.3217 · Cited by 30
“M1 polarization is initiated by high levels of INF‐γ, TNF‐ α, and IL‐6 (Krzyszczyk et al., 2018; Novak & Koh, 2013) which we did not detect at any time point.”
BackgroundThe role of inflammation in intravenous immune globulin–mediated hemolysis
Pendergrast, J. M., Willie‐Ramharack, K., Sampson, L., et al. (2015) · Transfusion · doi:10.1111/trf.13097 · Cited by 30
“Alternatively, polarization toward an M2 monocyte phenotype could trigger a “scavenging” response, which may be important in immune-mediated hemolysis.(6) It has been found, for example, that the low-affinity FccRIII receptor typically associated with M2 polarization is central to the clearance of IgG-opsonized RBCs i…”
BackgroundLow-intensity vibrations accelerate proliferation and alter macrophage phenotype in vitro
Pongkitwitoon, S., Weinheimer-Haus, E. M., Koh, T. J., & Judex, S. (2016) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2016.01.027 · Cited by 31
Self-citationLai, W., Xian, C., Chen, M., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110509 · Cited by 29
Depletion of Hepatic Macrophages Aggravates Liver Lesions Induced in Rats by Thioacetamide (TAA)
Golbar, H. M., Izawa, T., Wijesundera, K. K., Bondoc, A., Tennakoon, A. H., Kuwamura, M., & Yamate, J. (2016) · Toxicologic Pathology · doi:10.1177/0192623315621191 · Cited by 29
“M2 macrophages release anti-inflammatory cytokines (IL-4 and IL-10), which contribute to the resolution of inflammation by phagocytizing apoptotic cells and synthesizing growth factors (TGF-b1) important in tissue remodeling (La Flamme et al. 2012; Marti- nez 2011; Novak and Koh 2013).”
BackgroundSaliva initiates the formation of pro-inflammatory macrophages in vitro
Pourgonabadi, S., Müller, H., Mendes, J. R., et al. (2016) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2016.10.012 · Cited by 29
Proliferation of Ly6C+ monocytes/macrophages contributes to their accumulation in mouse skin wounds
Pang, J., Urao, N., & Koh, T. J. (2019) · Journal of Leukocyte Biology · doi:10.1002/jlb.3hi1119-389rrrr · Cited by 30
Self-citationTonEBP suppresses IL-10-mediated immunomodulation
Choi, S. Y., Lee, H. H., Lee, J. H., Ye, B. J., Yoo, E. J., Kang, H. J., Jung, G. W., An, S. M., Lee‐Kwon, W., Chiong, M., et al. (2016) · Scientific Reports · doi:10.1038/srep25726 · Cited by 27
Che, X., Park, K. C., Park, S. J., Kang, Y. H., Jin, H. A., Kim, J. W., Seo, D. H., Kim, D. K., Kim, T. I., Kim, W. H., et al. (2018) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00027.2018 · Cited by 28
“M2 macrophages express various factors that are important for tissue repair (23).”
BackgroundCheng, Y., Yang, C., Luo, D., Li, X., Le, X. C., & Rong, J. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000491651 · Cited by 28
CCL28‐induced CCR10/eNOS interaction in angiogenesis and skin wound healing
Chen, Z., Haus, J. M., Chen, L., Wu, S., Urao, N., Koh, T. J., & Minshall, R. D. (2020) · The FASEB Journal · doi:10.1096/fj.201902060r · Cited by 27
Self-citationDownregulation of nutrition sensor GCN2 in macrophages contributes to poor wound healing in diabetes
Hou, Y., Wei, D., Zhang, Z., Lei, T., Li, S., Bao, J., Guo, H., Tan, L., Xie, X., Zhuang, Y., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113658 · Cited by 30
Eren, A. D., Sinha, R., Eren, E. D., Yuan, H., İz, S. G., Valster, H., Moroni, L., Foolen, J., & de Boer, J. (2020) · Journal of Immunology and Regenerative Medicine · doi:10.1016/j.regen.2020.100027 · Cited by 26
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“M2 macrophages are also capable of producing ECM components [47] and may have contributed to the ECM related pathways which were overrepresented in response to MOK124.”
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A Novel CD206 Targeting Peptide Inhibits Bleomycin Induced Pulmonary Fibrosis in MicePreprint
Ghebremedhin, A., Salam, A. B., Adu-Addai, B., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.27.218115 · Cited by 27
“Several studies have demonstrated that activated CD206 positive M2 macrophages in fibrotic lesions, produce high amounts IL-10, IL-6, TNF-α, and TGF-β1 that enhance collagen synthesis and deposition [11, 12].”
BackgroundMacrophage phenotype is determinant for fibrosis development in keloid disease
Dirand, Z., Maraux, M., Tissot, M., Chatelain, B., Supp, D. M., Viennet, C., Perruche, S., & Rolin, G. (2024) · Matrix Biology · doi:10.1016/j.matbio.2024.03.001 · Cited by 31
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Metadata
- Authors
- Novak, M. L., & Koh, T. J.
- Affiliations
- University of Illinois Chicago (US)
- Corresponding author
- Koh, Timothy J
- ORCID
- Koh, Timothy J
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-03-15
- Volume
- 93
- Issue
- 6
- Pages
- 875-881
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- PMC
- PMC3656331
- OpenAlex
- W2159442019
- Semantic Scholar
- 32d24c1f92ce6e25fe1a62057f0c92ea3227742b
- Cited by
- 658
- References
- 85
- Citations by year
- 2026: 29 · 2025: 52 · 2024: 61 · 2023: 47 · 2022: 59 · 2021: 75 · 2020: 50 · 2019: 46 · 2018: 45 · 2017: 47 · 2016: 54 · 2015: 52 · 2014: 29 · 2013: 10
- FWCI
- 8.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Defense (#W81XWH-05-1-0159)
- U.S. National Institutes of Health (#R01GM092850)
- American College of Sports Medicine Doctoral Student Research (#2011-03604-00-00)
- University of Illinois at Chicago Graduate College Dean’s Scholar Award
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- macrophage phenotype, tissue repair, M1 macrophages, M2 macrophages, wound healing, macrophage heterogeneity, macrophage polarization, inflammatory macrophages, anti-inflammatory macrophages, fibrosis, macrophage markers
- MeSH terms
- Animals, Humans, Macrophages, Phenotype, Regeneration, Wound Healing
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