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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
36 Own interpretation · 33 Not checked yet · 11 No basis given · 1 Own result
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
plaindirect- Asserted: passes — The authors put it forward as true.
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In 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]
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In 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
hedged- Asserted: passes — The authors put it forward as true.
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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, 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
plain- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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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
“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
plain- Asserted: passes — The authors put it forward as true.
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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
“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
hedged- Asserted: passes — The authors put it forward as true.
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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
“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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably 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
plain- Asserted: passes — The authors put it forward as true.
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It 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
plain- Asserted: passes — The authors put it forward as true.
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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
“two of the best-characterized in vitro phenotypes are a proinflammatory”
§ Macrophage phenotypes during tissue repair > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably 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]
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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It 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
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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
“In numerous physiological and pathological states, Mp exhibit extensive heterogeneity and plasticity, and tissue repair is no exception.”
§ Macrophage phenotypes during tissue repair > Introduction
plain- Asserted: passes — The authors put it forward as true.
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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
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It 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
hedged- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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- 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
plaindirect- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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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
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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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
plain- Asserted: passes — The authors put it forward as true.
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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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably 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
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“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
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
“TGF- increases with time (skin); IL-10 time course not known.”
§ Macrophage phenotypes during tissue repair > Mp PHENOTYPES DURING TISSUE REPAIR AND FIBROSIS
“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].”
Citations
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Cited by
Sorted by citations
Items 401–500 of 654
Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model
Calle, P., Játiva, S., Torrico, S., et al. (2021) · Cells · doi:10.3390/cells10071650 · Cited by 12
“Macrophage dynamics during the different phases of CKD progression are not fully known, and assessment of the predominant macrophage phenotype may be relevant in terms of defining the type of therapy [13].”
BackgroundDong, J., Wu, B., & Tian, W. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1075233 · Cited by 15
“Previous studies mainly focused on the phenotypeswitching and the inflammatory regulation of macrophages under biomaterial stimulation (Novak and Koh, 2013; Jetten et al., 2014; Jetten et al., 2014; Spiller et al., 2014; Gurevich et al., 2018; Deng et al., 2019).”
Background5-Lipoxygenase contributes to PPARγ activation in macrophages in response to apoptotic cells
von Knethen, A., Sha, L. K., Kuchler, L., et al. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.08.045 · Cited by 12
Inflammation and cutaneous nervous system involvement in hypertrophic scarring
Hu, X., Li, S., Yang, H.-L., et al. (2015) · Neural Regeneration Research · doi:10.4103/1673-5374.167769 · Cited by 12
“Although acute inflammation is necessary for normal wound repair, chronic inflammation can lead to pathological fibrosis (Semlali et al., 2010; Wang and Zhao, 2010; Oh et al., 2011; Novak and Koh, 2013; Weisser et al., 2013; Wise et al., 2013; Niu et al., 2014).”
BackgroundKumar, S., Babiarz, J. P., Basak, S., Kim, J. H., Barminko, J., Gray, A., Mendapara, P., Schloss, R. S., Yarmush, M. L., & Grumet, M. (2015) · Nano LIFE · doi:10.1142/s179398441550004x · Cited by 12
The class D scavenger receptor CD68 contributes to mouse chronic liver injury
Yang, L., Yang, L., Dong, C., et al. (2018) · Immunologic Research · doi:10.1007/s12026-018-9002-y · Cited by 12
“which in vitro can be broadly classified as M1 (classical) or M2 (alternative) type [11].”
BackgroundIn vitro biocompatibility and wound healing properties of latex proteins dressing
Nunes, M. O., de Souza, T. D. F. G., Pierdoná, T. M., Ramos, M. V., Ferreira, K. Q., Duarte, R. S., Shahwar, D., Wilke, D. V., Wong, D. V. T., & de Alencar, N. M. N. (2021) · Toxicology in Vitro · doi:10.1016/j.tiv.2021.105230 · Cited by 13
Dzobo, K., Wilgus, T. A., Zamora-Mora, V., Zoncsich, A., de Mezerville, R., Khumalo, N. P., & Bayat, A. (2025) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2025.1668930 · Cited by 11
“As the wound healing process progresses, there is a shift towards a predominance of M2 macrophages, which promotes tissue repair and resolution of in fl ammation (Novak and Koh, 2013).”
Amin, A., Akhtar, M. S., Khalil, A. A. K., Ali, S., & Zaman, W. (2025) · Medicinal Chemistry Research · doi:10.1007/s00044-025-03508-z · Cited by 17
“M1 macrophages secrete high levels of pro-in fl ammatory cytokines, including TNF-α , IL-6, and IL-1 β , which exacerbate in fl ammatory responses [96, 97].”
The yeast–human coevolution: Fungal transition from passengers, colonizers, and invaders
Nenciarini, S., Renzi, S., Paola, M. D., Meriggi, N., & Cavalieri, D. (2023) · WIREs Mechanisms of Disease · doi:10.1002/wsbm.1639 · Cited by 12
Future Directions About Keloid Scars Based on Pathogenesis and Therapies
Zhang, G., Liu, Z., Li, Z., & Xu, Y. (2024) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s470650 · Cited by 12
Ayalew, H., Xu, C., Adane, A., Sánchez, A. L. B., Li, S., Wang, J., Wu, S., Qiu, K., Qi, G., & Zhang, H. (2024) · Poultry Science · doi:10.1016/j.psj.2024.104607 · Cited by 13
“…contribute to immune tolerance by aiding regulatory T cell differentiation and suppressing excessive inflammation (Zigmond et al., 2012 During pathogen exposure, macrophages adopt one of two main phenotypes: M1 or M2 (Sica and Mantovani, 2012; Novak and Koh, 2013; Martinez and Gordon, 2014).”
Anti-Inflammatory Effects of Hydrogen Sulfide in Axes Between Gut and Other Organs
Lu, W., & Wen, J. (2024) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0531 · Cited by 14
“The bene fi cial effect of H 2 S in RA seems to be dose-dependent; low concentration of H 2 S inhibits the activation and synthesis of proin fl ammatory mediators (NF-j B, IL-6, TNF-a , and IL-1 b ) released from murine macrophages in the presence of LPS (Whiteman, et al., 2010).”
InfluentialJanani, G., Zhang, L., Badylak, S. F., & Mandal, B. B. (2022) · Biomaterials Advances · doi:10.1016/j.bioadv.2022.213223 · Cited by 12
The many shades of macrophages in regulating transplant outcome
Chen, S., Lakkis, F. G., & Li, X. C. (2020) · Cellular Immunology · doi:10.1016/j.cellimm.2020.104064 · Cited by 11
Nakagomi, T., Tanaka, Y., Nakagomi, N., Matsuyama, T., & Yoshimura, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176360 · Cited by 11
Ji, H., Sukarto, A., Deegan, D. B., & Fan, F. (2021) · Plastic & Reconstructive Surgery Global Open · doi:10.1097/gox.0000000000003420 · Cited by 11
Freestanding Magnetic Microtissues for Tissue Engineering Applications
Santos, L. F., Patrício, S. G., Silva, A. S., & Mano, J. F. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202101532 · Cited by 11
Hayashi, Y., Kawamura, R., Nishimatsu, S., Fukuta, O., & Nakashima, M. (2018) · Rejuvenation Research · doi:10.1089/rej.2018.2064 · Cited by 11
“22 Following the early inflammatory reaction, M1 macrophages shift to M2 macrophages and polarize, 31,32 with which chemical mediators secreted also change.”
Lei, X., Cheng, L., Yang, Y., Pang, M., Dong, Y., Zhu, X., Chen, C., Yao, Z., Wu, G., Cheng, B., et al. (2021) · Burns & Trauma · doi:10.1093/burnst/tkab033 · Cited by 12
“In the early inflammatory phase, M1 pro-inflammatory macrophages are attracted to the wound site to produce proinflammatory cytokines, including IL-6, TNF-α and other stimulators that accelerate the initial stages of wound healing [50].”
BackgroundLiu, H., Sun, C., Jiang, Y., Gao, R., Ying, Q., Li, X., Liu, H., Guo, J., & Li, M. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.113894 · Cited by 11
Dermal macrophage and its potential in inducing hair follicle regeneration
Gao, Y., Wang, J., Zhu, D., Miao, Y., & Hu, Z. (2021) · Molecular Immunology · doi:10.1016/j.molimm.2021.02.021 · Cited by 12
A high-fat diet has negative effects on tendon resident cells in an in vivo rat model
Bolam, S. M., Konar, S., Park, Y. E., Callon, K. E., Workman, J., Monk, A. P., Coleman, B., Cornish, J., Vickers, M. H., Munro, J. T., et al. (2022) · International Orthopaedics · doi:10.1007/s00264-022-05340-1 · Cited by 10
Richards, J. H., Freeman, D. D., & Detloff, M. R. (2023) · Journal of Pain · doi:10.1016/j.jpain.2023.11.016 · Cited by 11
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“10,50,51 This study elucidates multi-tiered mechanisms by which V g 4 + gd T cells calibrate macrophage activation phenotypes during skin repair through sophisticated IFN-g conditioning.”
BackgroundZakeri, A., Everts, B., Williams, A. R., & Nejsum, P. L. (2022) · Cytokine · doi:10.1016/j.cyto.2022.155919 · Cited by 10
Margulies, B. S., DeBoyace, S. D., Parsons, A. M., Policastro, C. G., Ee, J. S. S., & Damron, T. A. (2014) · Journal of Orthopaedic Research® · doi:10.1002/jor.22790 · Cited by 9
“Significant infiltration of cells that stained with CD14, tomato lectin, CD206, and Arg1 were observed, which suggests the presence of an M2-macrophage.26 In contrast, cells observed within the HFF tissue failed to express significant levels of iNOS, CD16 or B7–2, which are markers of the M1-macrophage phenotype.”
BackgroundInterferon‐γ, but Not Interleukin‐4, Suppresses Experimental Polymyositis
Yoshihashi‐Nakazato, Y., Kawahata, K., Kimura, N., Miyasaka, N., & Kohsaka, H. (2016) · Arthritis & Rheumatology · doi:10.1002/art.39592 · Cited by 10
“polarizes them to the alternatively activated macrophage phenotype (30).”
BackgroundThrombospondin-1 and disease progression in dysferlinopathy
Urao, N., Mirza, R. E., Corbiere, T. F., et al. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx378 · Cited by 10
Self-citationPapazova, D. A., Krebber, M. M., Oosterhuis, N. R., Gremmels, H., van Zuilen, A. D., Joles, J. A., & Verhaar, M. C. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.035030 · Cited by 10
“Anti-eGFP/ ED1 double staining (1:200 for both, mouse anti-rat CD68, ab31630, 1:250; Abcam) was used to count all recipient-derived (eGFP+/ED1+) and donorderived (eGFP−/ED1+)MQs in post-Tx kidneys.”
BackgroundInfluentialInnovations and Emerging Therapies to Combat Renal Cell Damage: NAD + As a Drug Target
Manrique‐Caballero, C. L., Kellum, J. A., Gómez, H., Franco, F., Giacchè, N., & Pellicciari, R. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2020.8066 · Cited by 10
“…these pattern recognition receptors triggers a downstream cascade of signals that will end activating the nuclear factor-kappa B (NF-j B), a transcription factor which main function is to upregulate the gene expression of in-flammatory cytokines and recruit immune cells to the site of injury (76).”
Mechanotherapy: Modulating immune cell function in tissue regeneration and fibrosis
Ward, N. A., Prendeville, H., Wallace, E. J., Shokrani, P., Trask, L., Dillon, R., Beatty, R., Roche, E. T., Duffy, G. P., & Dolan, E. B. (2025) · Acta Biomaterialia · doi:10.1016/j.actbio.2025.08.048 · Cited by 10
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“…it is important to recognize that these essential, nervous system-specific immune cells are involved in a multifaceted array of functions encom - passing brain development, neural environment mainte - nance, injury response, and the repair process (Novak & Koh, 2013 ; Shechter et al., 2013 ).”
Barilo, J., Ratsimor, M., Chan, A., Hembruff, H., & Basta, S. (2025) · Frontiers in Bioscience-Landmark · doi:10.31083/fbl27638 · Cited by 10
Mallis, P., Michalopoulos, Ε., Sarri, E.-F., Papadopoulou, E. P., Theodoropoulou, V., Katsimpoulas, M., & Stavropoulos‐Giokas, C. (2022) · Current Issues in Molecular Biology · doi:10.3390/cimb44100303 · Cited by 10
Kim, I. ‐., Park, H. C., Quan, H., Kim, Y., Wu, L., & Yang, H. (2019) · International Endodontic Journal · doi:10.1111/iej.13088 · Cited by 9
“Macrophages were known to polarize into two phenotypes, M1 and M2 [13].”
BackgroundChaudhari, A. A., Kim, W. H., & Lillehoj, H. S. (2019) · Poultry Science · doi:10.1016/j.psj.2019.10.023 · Cited by 9
Water-filtered Infrared A (wIRA) Irradiation
Vaupel, P. W. (2022) · Springer eBooks · doi:10.1007/978-3-030-92880-3 · Cited by 10
Coupling Osmotic Efficacy with Biocompatibility in Peritoneal Dialysis: A Stiff Challenge
Bonomini, M., Masola, V., Monaco, M. P., Sirolli, V., Liberato, L. D., Prosdocimi, T., & Arduini, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063532 · Cited by 9
“…PD solution, were able to preserve MCs and the PM, with fewer cells in the peritoneal surface tissue testing positive for proliferation, apoptosis and vimentin, together with a dominant presence in the peritoneum of M2 macrophages, which have remodeling/healing actions in damaged tissues [71].”
BackgroundLuo, B., Ding, X., Yue, H., et al. (2024) · Molecular Immunology · doi:10.1016/j.molimm.2024.12.002 · Cited by 8
Li, L. (2025) · Frontiers in Drug Delivery · doi:10.3389/fddev.2025.1598145 · Cited by 8
“The subsequent immune phase (24 – 72 h post-injury) involves neutrophils clearing debris and macrophages polarizing from pro-immune (M1) to anti-immune (M2) phenotypes, resolving in fl ammation and initiating tissue repair (Novak and Koh, 2013).”
Liu, H.-J., Diesler, R., Chami, J., Wu, B., Du, H., Jin, Y., Daou, M., Alesi, N., Khabibullin, D., Leroux, C., et al. (2025) · European Respiratory Journal · doi:10.1183/13993003.00084-2025 · Cited by 8
Hou, Y., Zhao, T., Guo, Y., & Shi, J. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152489 · Cited by 12
Zhou, X., Feng, Z., Liu, P., Song, Y., Shakir, I., Sun, X., Xie, H., & Li, W. (2025) · Advanced Healthcare Materials · doi:10.1002/adhm.202503944 · Cited by 10
Anatomy of the Skin and Pathophysiology of Radiation Dermatitis
Arron, S. T. (2016) · Springer eBooks · doi:10.1007/978-3-319-31460-0_2 · Cited by 8
Wound healing in Mac‐1 deficient mice
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“As the wound heals and enters the stages of cellular proliferation and remodeling, macrophages adopt a reparative phenotype (often termed M2 or alternatively activated macrophages), producing factors that support tissue growth and reduce inflammation.(11,12) Several studies have demonstrated that macrophage function i…”
BackgroundGeurtzen, K., López-Delgado, A. C., Duseja, A., Kurzyukova, A., & Knopf, F. (2022) · Development · doi:10.1242/dev.199803 · Cited by 11
Schilling, B. K., Baker, J. S., Komatsu, C., Turer, D. M., Bengür, F. B., Nerone, W. V., Qin, F., Cottrill, A. R., Kokai, L. E., Rubin, J. P., et al. (2022) · Plastic & Reconstructive Surgery · doi:10.1097/prs.0000000000010115 · Cited by 8
van Balen, P., van der Zouwen, B., Kruisselbrink, A. B., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00331 · Cited by 8
“High expression of CD206 on HLA class II-positive cells was found, which is predominantly present on macrophages playing a role in later stages of tissue repair in the skin and in the remodeling phase (19).”
BackgroundDeng, X., Li, X., Huang, G., et al. (2025) · Biology of Reproduction · doi:10.1093/biolre/ioaf061 · Cited by 7
Tai Chi and Its Impact on Immune Mechanisms: A Comprehensive Review
Thelander, Y. Z., & Ring, H. Z. (2025) · Health · doi:10.4236/health.2025.175033 · Cited by 7
A Macrophage‐Based Cell Therapy Approach Promotes Collagen Deposition in Diabetic Wounds
Boodhoo, K., Vlok, M., & van de Vyver, M. (2025) · Wound Repair and Regeneration · doi:10.1111/wrr.70071 · Cited by 7
“There are, however, several drawbacks associated with the phenotypic diversity of these cells and their sensitivity to the toxic pathological wound micro-environments, making the outcome of cell therapy approaches unpredictable [18, 20].”
The Yin-Yang functions of macrophages in metabolic disorders
Bai, J., & Liu, F. (2022) · Life Medicine · doi:10.1093/lifemedi/lnac035 · Cited by 7
A mathematical model and numerical simulation for SARS-CoV-2 dynamics
Amoddeo, A. (2023) · Scientific Reports · doi:10.1038/s41598-023-31733-2 · Cited by 10
Novel HALO ® image analysis to determine cell phenotype in porous precision‐templated scaffolds
Chan, N. R., Hwang, B., Waworuntu, R. L., Tran, A. J., Ratner, B. D., & Bryers, J. D. (2023) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37547 · Cited by 8
Gopalakrishnan, B., Galili, U., Saenger, M., Burket, N. J., Koss, W. A., Lokender, M. S., Wolfe, K. M., Husak, S. J., Stark, C. J., Solorio, L., et al. (2024) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-023-00616-y · Cited by 7
“This timing of macrophage tapering is consistent with other reports [5, 9, 53–55].”
Renal fibrosis due to multiple cisplatin treatment is exacerbated by kinin B1 receptor antagonism
Budu, A., Freitas‐Lima, L. C., Arruda, A. C., et al. (2021) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x2021e11353 · Cited by 7
“M1 are considered pro-inflammatory macrophages, and produce cytokines such as IL-1, IL-6, and TNF-a, whereas M2 are considered anti-inflammatory macrophages, and produce mannose receptor, IL-10, and IL-4 (23,24).”
BackgroundNutritional Regulation of Mammary Tumor Microenvironment
Thakkar, N., Shin, Y. B., & Sung, H. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.803280 · Cited by 7
“In comparison, classical CD206+ M2-like macrophages are anti-inflammatory, contributing to tissue repair and production of antiinflammatory cytokines such as IL-4 and IL-13 (Novak and Koh, 2013).”
BackgroundExpression of intercellular adhesion molecule‐1 by myofibers in mdx mice
Torres‐Palsa, M. J., Koziol, M., Goh, Q., Cicinelli, P. A., Peterson, J. M., & Pizza, F. X. (2015) · Muscle & Nerve · doi:10.1002/mus.24626 · Cited by 7
Heim, C., Motsch, B., Jalilova, S., Bernhardt, W. M., Ramsperger-Gleixner, M., Burzlaff, N. I., Weyand, M., Eckardt, K., & Ensminger, S. M. (2016) · Transplant Immunology · doi:10.1016/j.trim.2016.08.007 · Cited by 7
Preparation of polymer microspheres capable for pioglitazone release to modify macrophages function
Momotori, N., Jo, J.-I., & Tabata, Y. (2019) · Regenerative Therapy · doi:10.1016/j.reth.2019.06.008 · Cited by 7
“On the other hand, M2 macrophages with alternative non-in fl ammatory functions promote the responses of type 2 helper Tcells associated with tumor progression [2], parasite infections, tissue repair [3,4], and debris removal [4 e 7].”
BackgroundPotential Role of CXCL10 in Monitoring Response to Treatment in Leprosy Patients
Ferreira, H., Mendes, M. A., Barbosa, M. G. D. M., de Oliveira, E. B., Sales, A. M., Moraes, M. O., Sarno, E. N., & Pinheiro, R. O. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.662307 · Cited by 6
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“In contrast, M2 macrophages express arginase, which hydrolyses arginine into ornithine and urea, which can contribute to tissue repair and cell proliferation by producing polyamines and proline from ornithine [17].”
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“Conversely, M2-phenotype macrophages produce anti-inflammatory cytokines and promote tissue remodeling and repair [7].”
BackgroundRegulatory macrophages in solid organ xenotransplantation
Hoang, T. X., & Kim, J. Y. (2023) · Korean Journal of Transplantation · doi:10.4285/kjt.23.0055 · Cited by 10
“M2d macrophages, also referred to as tumor-as - sociated macrophages, are induced by A2 adenosine receptor agonists or IL-6 [62,76-78].”
BackgroundRegenerative loss in the animal kingdom as viewed from the mouse digit tip and heart
Tan, F. H., & Bronner-Fraser, M. E. (2023) · Developmental Biology · doi:10.1016/j.ydbio.2023.12.008 · Cited by 7
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“26,27 The results showed that Arg1-positive cells were rarely detected in normal control lungs and were abundantly increased in fibrotic lungs on days 7 and 14 (Fig.”
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“Macrophages present during tissue repair are not a single homogenous population but encompass a temporally regulated spectrum of activation states [48].”
Borage oil attenuates progression of cardiac remodeling in rats after myocardial infarction
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α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State
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Preparation of a nitric oxide imaging agent from gelatin derivative micelles
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Early Macrophage Activation in Preterm Newborns and Respiratory Disease
Milan, À., Priante, E., Nardo, D., Tosato, F., Pantano, G., Baraldi, E., & Zaramella, P. (2017) · Journal of Child Science · doi:10.1055/s-0037-1605579 · Cited by 6
Expression of CD 163 in hereditary gingival fibromatosis: A possible association with TGF ‐β1
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“This finding can be involved in the compression of blood vessels with a subsequent local ischemia, resulting in the switch of the macrophages from M1 to M2.”
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“In this case, tissue repair may be linked to the decrease in proin fl ammatory mediators in skin cells, such as IFN-γ and CXCL10 ( Ferreira et al., 2021 ; Novak & Koh, 2013 ).”
BackgroundResearch progress on the role of macrophages in acne and regulation by natural plant products
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“…production of proteolytic enzymes (e.g., matrix metalloproteinases), leading to collagen fi ber degradation, impaired recombination, and subsequent alterations in local skin tissue structure during the reparative phase of post-acne erythema, ultimately resulting in scar formation (122, 123).”
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Machine learning-based label-free macrophage phenotyping in immune-material interactions
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Macrophages Fuel Skeletal Muscle Regeneration
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“Irrespective, it is well accepted that macrophages can promote tissue repair trough the clearance of dead cells, induction of angiogenesis, and regulation of matrix remodeling [2].”
BackgroundThe experimental study of TNF-α & CRP expression in the spinal tuberculosis after instrumentation
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Characterization of the macrophage infiltrate in a case of xanthogranulomatous pyelonephritis
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“AAM produces IL-10, arginase and many extracellular molecules that play a crucial role in intestinal homeostasis and tissue repair [40,41].”
BackgroundInfluentialEcballium elaterium extract reduces fibrosis during wound healing in rats
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“The M2a subset is often referred to as ‘wound healing’ macrophages, as it refers to factors important for tissue repair [17].”
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“Мф М2 типа, в свою очередь, секретируют цитокины CCLК7, CCL22, CCL24, трансформирующий фактор роста-β (TGF-β), тромбоцитарный фактор роста (PDGF), фактор роста фибробластов 2 (FGF-2) и другие профибротические цитокины, и представляют на своей поверхности такие поверхностные маркеры, как CD163, стабилин-1 [28, 36, 39,…”
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Chronic intermittent hypoxia drives M1 macrophage polarization in dorsal root ganglia
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“M1 macrophages exhibit an inflammatory phenotype characterized by high expression of surface markers such as CD80, CD86, and MHC-II, along with production of proinflammatory cytokines (Novak and Koh, 2013; Tardito et al., 2019; Tarique et al., 2015).”
Acupuncture accelerates wound healing via CGRP-RAMP1-TSP1-mediated macrophage M2 polarization
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“M2 macrophages are widely recognized as pro-repair cells that express a range of healing-related factors, including arginase-1, ECM components, and growth factors such as VEGF-A, PDGF, and IGF [24].”
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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