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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.
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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
“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.
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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
“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
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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]
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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.
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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].”
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Promoting tissue regeneration by modulating the immune system
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Titanium surface characteristics, including topography and wettability, alter macrophage activation
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“Macrophages are responsible for the initial immune response, inflammation, and maintaining tissue homeostasis [3, 8, 9].”
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Current Advances in Immunomodulatory Biomaterials for Bone Regeneration
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Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds
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BackgroundTailoring Materials for Modulation of Macrophage Fate
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The big five in fibrosis: Macrophages, myofibroblasts, matrix, mechanics, and miscommunication
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Macrophage-Mediated Inflammation in Skin Wound Healing
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“Despite the predominantly proinflammatory cytokine profile of monocytes/macrophages during the early inflammatory phase, these cells are not fully analogous to in vitroedefined M1 macrophages.(12,13) For instance, early mouse skin wound monocytes/macrophages express high levels of arginase-1 and Ym1,(22,45) which are…”
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“Generally speaking, macrophages are dichotomized into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes based on their activity during tissue repair processes (Novak and Koh, 2013).”
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Macrophage Related Chronic Inflammation in Non-Healing Wounds
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“with downregulated inflammatory factors and upregulated antiinflammatory cytokines, including TGF-b, IL-10, and growth factors, such as platelet-derived growth factors (PDGF), resistinlike molecule-a (Relma), epidermal growth factor, and vascular endothelial growth factor-a (Vegfa), that drive tissue repair (18, 20, 4…”
BackgroundTumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy
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BackgroundRole of macrophages in peripheral nerve injury and repair
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Acute Inflammation in Tissue Healing
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BackgroundMacrophages provide a transient muscle stem cell niche via NAMPT secretion
Ratnayake, D., Nguyen, P. D., Rossello, F. J., Wimmer, V. C., Tan, J. L., Galvis, L. A., Julier, Z., Wood, A. J., Boudier, T., Isiaku, A. I., et al. (2021) · Nature · doi:10.1038/s41586-021-03199-7 · Cited by 239
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The multicellular complexity of peripheral nerve regeneration
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Macrophage Differentiation in Normal and Accelerated Wound Healing
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“The final remodeling phase involves collagen remodeling (Novak and Koh 2013).”
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Role of Fibroblast Populations in Periodontal Wound Healing and Tissue Remodeling
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“These cells are sequentially recruited into the wound at the beginning and end of the inflammatory phase, respectively (Novak and Koh, 2013).”
BackgroundFrom Inflammation to Current and Alternative Therapies Involved in Wound Healing
Serra, M. B., Barroso, W. A., da Silva, N. N., Silva, S. D. N., Borges, A. C. R., Abreu, I. C., & Borges, M. O. D. R. (2017) · International Journal of Inflammation · doi:10.1155/2017/3406215 · Cited by 208
“In contrast, cytokines, such as IL-4 and IL-13, lead to macrophages formation of the M2 subset, which regulate inflammation by expressing mediators as IL-1 receptor antagonist (IL-1R), IL1 type II receptor, transforming growth factor-β (TGF-β), vasopressin endothelial growth factor (VEGF), and insulinlike growth facto…”
Nanoparticle clearance is governed by Th1/Th2 immunity and strain background
Jones, S. W., Roberts, R. A., Robbins, G. R., Perry, J. L., Kai, M. P., Chen, K., Bo, T., Napier, M. E., Ting, J. P. ‐., DeSimone, J. M., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66895 · Cited by 202
Cosín‐Roger, J., Ortiz‐Masiá, D., Calatayud, S., Hernández, C., Esplugues, J. V., & Barrachina, M. D. (2015) · Mucosal Immunology · doi:10.1038/mi.2015.123 · Cited by 200
“The early expression observed in iNOS and CD11c, as well as that of two hallmark indicators of M2 activation (ArgI and Ym1), suggests that macrophages in the inflammatory phase of intestinal repair adopt a combination of M1 and M2 phenotypes similar to that reported in other tissues.(15,16,43) At 4 days after TNBS, th…”
BackgroundResultCD301b+ Macrophages Are Essential for Effective Skin Wound Healing
Shook, B. A., Xiao, E., Kumamoto, Y., Iwasaki, A., & Horsley, V. (2016) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2016.05.107 · Cited by 186
“The nature of the myeloid cell plasticity during tissue repair is not clear (Gordon and Taylor, 2005; Novak and Koh, 2013).”
Drug delivery, cell-based therapies, and tissue engineering approaches for spinal cord injury
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Rethinking Regenerative Medicine: A Macrophage-Centered Approach
Brown, B. N., Sicari, B. M., & Badylak, S. F. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00510 · Cited by 196
“During the granulation tissue formation and wound contraction phase of cutaneous wound healing at 7–10 days post-injury, paracrine effector molecules, including cytokines such as IL-10 and growth factors such as VEGF, PDGF-β, and TGF-β, produced by M2 macrophages recruit fibroblasts into the wound site and promote myo…”
BackgroundInfluentialLi, J., Wen, J., Li, B., Wan, L., Qiao, W., Shen, J., Jin, W., Jiang, X., Yeung, K., & Chu, P. K.-H. (2017) · Advanced Science · doi:10.1002/advs.201700678 · Cited by 184
Xu, M. L., Li, X., & Song, L. (2020) · Pharmaceutical Biology · doi:10.1080/13880209.2020.1779318 · Cited by 184
“(A) The mRNA levels of macrophage M1 biomarkers (iNOS, IL-1b and IL-6) were examined by qRT-PCR.”
BackgroundInfluentialRetractedThe neuroimmunology of degeneration and regeneration in the peripheral nervous system
Oranburg, T. D., Lindborg, J. A., Niemi, J. P., & Zigmond, R. E. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.09.027 · Cited by 180
“Regardless of the differing hypotheses concerning the macrophage activation state after nerve injury, it may be that macrophages involved in tissue repair encompass a spectrum of activation states throughout the repair process (for review see Novak and Koh, 2013).”
Peptides as Therapeutic Agents for Inflammatory-Related Diseases
Manna, S. L., Natale, C. D., Florio, D., & Marasco, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092714 · Cited by 183
“NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) is a protein complex that controls transcription of DNA and plays a key role in inflammation; normally, it localizes in the cytoplasm, but under inflammatory conditions, it translocates into the nucleus where it regulates the pro-inflammatory gene…”
BackgroundMacrophages in the Aging Liver and Age-Related Liver Disease
Stahl, E. C., Haschak, M. J., Popovic, B., & Brown, B. N. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02795 · Cited by 171
“M2-polarized macrophages typically appear following M1-polarized macrophages in an injury setting and serve as a counterbalance to resolve inflammation and promote tissue repair (34).”
BackgroundSaldaña, L., Bensiamar, F., Vallés, G., Mancebo, F. J., García‐Rey, E., & Vilaboa, N. E. (2019) · Stem Cell Research & Therapy · doi:10.1186/s13287-019-1156-6 · Cited by 174
Regulatory T cells in skin injury: At the crossroads of tolerance and tissue repair
Boothby, I. C., Cohen, J. N., & Rosenblum, M. D. (2020) · Science Immunology · doi:10.1126/sciimmunol.aaz9631 · Cited by 182
“IFN- activates macrophages toward an inflammatory phenotype analogous to classically activated (“M1”) macrophages described in vitro (64).”
BackgroundHuang, C., Wang, J., Liu, H., Huang, R., Yan, X., Song, M., Tan, G., & Zhi, F. (2022) · BMC Medicine · doi:10.1186/s12916-022-02352-x · Cited by 188
“TGFb enhances fibroblast proliferation and collagen production observed in macrophage/fibroblast co-cultures [46].”
BackgroundFunction of Macrophages in Disease: Current Understanding on Molecular Mechanisms
Zhang, C., Yang, M. J., & Ericsson, A. C. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.620510 · Cited by 181
Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics
Yin, B., Ni, J., Witherel, C. E., Yang, M., Burdick, J. A., Wen, C., & Wong, S. H. D. (2021) · Theranostics · doi:10.7150/thno.62708 · Cited by 168
“On the other hand, several leukocyte subsets, including M2 macrophages showing anti-inflammatory may initiate tissue repair and suppress fibrosis [129].”
BackgroundEgli, A., Santer, D. M., O’Shea, D., Tyrrell, D. L., & Houghton, M. (2014) · Emerging Microbes & Infections · doi:10.1038/emi.2014.51 · Cited by 166
“145, 146 Macrophages thus are positioned at the intersecting innate and adaptive immune responses continuously modulating the Th1 and Th2 cytokine balance during infection.”
BackgroundAmelioration of ulcerative colitis via inflammatory regulation by macrophage-biomimetic nanomedicine
Sun, T., Kwong, C. H. T., Cheng, G., Wei, J., Yue, L., Zhang, J., Ye, R. D., & Wang, R. (2020) · Theranostics · doi:10.7150/thno.48448 · Cited by 160
“M1 macrophages produce pro-inflammatory cytokines and ROS, whereas M2 macrophages secret anti-inflammatory cytokines, accelerate inflammation resolution and promote tissue repair [42, 43], thus M2 macrophage was previously leveraged for UC therapy [22].”
BackgroundEffects of CTGF Blockade on Attenuation and Reversal of Radiation-Induced Pulmonary Fibrosis
Bickelhaupt, S., Erbel, C., Timke, C., Wirkner, U., Dadrich, M., Flechsig, P., Tietz, A., Pföhler, J., Groß, W., Peschke, P., et al. (2016) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djw339 · Cited by 153
“by FG-3019 was reflected in the transcriptome by normalizing markers for mast cells and M2 polarized macrophages, but not M1 macrophages (Figure 5, B–D) (68,69).”
BackgroundM2 Macrophages as a Potential Target for Antiatherosclerosis Treatment
Bi, Y., Chen, J., Hu, F., Liu, J., Li, M., & Zhao, L. (2019) · Neural Plasticity · doi:10.1155/2019/6724903 · Cited by 158
“Researches show that the M2 phenotype could secrete anti-inflammatory factors [10], promote tissue remodeling and repair [11, 12], and clear dying cells and debris [13], thus contributing to atheroma therapy.”
BackgroundBai, J., Wang, H., Chen, H., Ge, G., Wang, M., Gao, A., Tong, L., Xu, Y., Yang, H., Pan, G., et al. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120197 · Cited by 156
Bevan, L., Lim, Z. W., Venkatesh, B., Riley, P. R., Martin, P. B., & Richardson, R. J. (2019) · Cardiovascular Research · doi:10.1093/cvr/cvz221 · Cited by 148
“sponse, the appropriate balance of these activation states is thought to be vital for optimal wound healing and could be harnessed to promote regeneration.(23,24) Graphical Abstract 1358 L.”
BackgroundReconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry
Notter, T., Coughlin, J. M., Sawa, A., & Meyer, U. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.232 · Cited by 151
Wound Chronicity, Impaired Immunity and Infection in Diabetic Patients
Rodríguez-Rodríguez, N., Martínez-Jiménez, I., Ojalvo, A. G., Mendoza‐Marí, Y., Guillén, G. E., Armstrong, D. G., & Berlanga‐Acosta, J. (2021) · MEDICC Review · doi:10.37757/mr2021.v23.n3.8 · Cited by 150
“…polarize to an M2 subpopulation with anti-in fl ammatory activity by expressing interleukin-receptor antagonists and a collection of fi broangiogenic growth factors that enhance fi broblast proliferation, extracellular matrix synthesis, angiogenesis,[59,60] ultimately reducing in fl ammation .”
BackgroundMareninova, O. A., Sendler, M., Malla, S. R., Yakubov, I., French, S. W., Tokhtaeva, E., Vagin, O., Oorschot, V. M. J., Lüllmann‐Rauch, R., Blanz, J., et al. (2015) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2015.07.006 · Cited by 143
Wermuth, P. J., & Jiménez, S. A. (2015) · Clinical and Translational Medicine · doi:10.1186/s40169-015-0047-4 · Cited by 141
“Monocytes and macrophages play a pivotal role in coordinating the various stages of the wound healing process by their ability to produce and secrete numerous growth factors, cytokines and other mediators capable of exerting paracrine effects on other cells in affected tissues [27,59-72,154-157].”
BackgroundMacrophages with regulatory functions, a possible new therapeutic perspective in autoimmune diseases
Benedetto, P. D., Ruscitti, P., Vadasz, Z., Toubi, E., & Giacomelli, R. (2019) · Autoimmunity Reviews · doi:10.1016/j.autrev.2019.102369 · Cited by 140
Preparation and Use of Decellularized Extracellular Matrix for Tissue Engineering
McInnes, A. D., Moser, M., & Chen, D. (2022) · Journal of Functional Biomaterials · doi:10.3390/jfb13040240 · Cited by 146
Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of COPD
Yamasaki, K., & van Eeden, S. F. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020582 · Cited by 145
“Induced by fungi, immunocomplexes, helminths, complement components, apoptotic cells, macrophage colony-stimulating factors, IL-4, and IL-13, M2 macrophages secrete anti-inflammatory cytokines, including IL-10, TGF-β, CCL18, and CCL22 [7], and are generally characterized by their high CD163 and CD206 expression levels…”
BackgroundMacrophage polarization states in atherosclerosis
Wu, J., He, S., Song, Z., Chen, S., Lin, X., Sun, H., Zhou, P., Peng, Q., Du, S., Zheng, S., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1185587 · Cited by 153
“Consequently, they are usually referred to as wound healing macrophages (29).”
BackgroundWang, J., Meng, F., Song, W., Jin, J., Ma, Q., Fei, D., Fang, L., Chen, L., Wang, Q., & Zhang, Y. (2018) · International Journal of Nanomedicine · doi:10.2147/ijn.s163956 · Cited by 137
“38 The wound and implant sites naturally contain a combination of stimuli that favor both M1 and M2 macrophage polarization at different stages of healing, 17,39 thus, from results of IHC staining, both iNOS-positive cells and CD163-positive cells could be found around the implants.”
Host response to synthetic mesh in women with mesh complications
Nolfi, A. L., Brown, B. N., Liang, R., Palcsey, S. L., Bonidie, M. J., Abramowitch, S. D., & Moalli, P. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2016.04.008 · Cited by 136
Regulation of decellularized matrix mediated immune response
Chakraborty, J., Roy, S., & Ghosh, S. (2020) · Biomaterials Science · doi:10.1039/c9bm01780a · Cited by 130
Sex-Specific T-Cell Regulation of Angiotensin II–Dependent Hypertension
Ji, H., Zheng, W., Li, X., Liu, J., Wu, X., Zhang, M. A., Umans, J. G., Hay, M., Speth, R. C., Dunn, S. E., et al. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.03663 · Cited by 137
Hao, S., Meng, J., Zhang, Y., Liu, J., Nie, X., Wu, F., Yang, Y., Wang, C., Gu, N., & Xu, H. (2017) · Biomaterials · doi:10.1016/j.biomaterials.2017.06.013 · Cited by 133
Innate immunity activation in the early brain injury period following subarachnoid hemorrhage
on behalf of the Canadian Critical Care Translational Biology Group, Gris, T., Laplante, P., Thébault, P., Cayrol, R., Najjar, A. A., Joannette-Pilon, B., Brillant-Marquis, F., Magro, E., English, S. W., et al. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1629-7 · Cited by 131
“These macrophages are reprogrammed in response to their microenvironment into several phenotypes ranging from pro-inflammatory to anti-inflammatory macrophages [40].”
BackgroundTran, T.-H., Rastogi, R., Shelke, J. D., & Amiji, M. M. (2015) · Scientific Reports · doi:10.1038/srep16632 · Cited by 138
The role of macrophages in the formation of hypertrophic scars and keloids
Xu, X., Gu, S., Huang, X., Ren, J., Gu, Y., Wei, C., Lian, X., Li, H., Gao, Y., Jin, R., et al. (2020) · Burns & Trauma · doi:10.1093/burnst/tkaa006 · Cited by 139
“The temporal changes in M1/M2 distribution occur in various tissue repair processes and fibrosis, including skin [30], kidney [31] and liver [32].”
BackgroundOsteoinduction and osteoimmunology: Emerging concepts
Miron, R. J., Bohner, M., Zhang, Y., & Bosshardt, D. D. (2023) · Periodontology 2000 · doi:10.1111/prd.12519 · Cited by 143
Attributes of alternatively activated (M2) macrophages
Shrivastava, R., & Shukla, N. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.03.062 · Cited by 132
Capote, J. C., Kramerova, I. A., Martinez, L., Vetrone, S. A., Barton, E. R., Sweeney, H. L., Miceli, M. C., & Spencer, M. J. (2016) · The Journal of Cell Biology · doi:10.1083/jcb.201510086 · Cited by 124
“JCB • Volume 213 • NumBer 2 • 2016 276 and reactive nitrogen and oxygen intermediates (Mantovani et al., 2007; Novak and Koh, 2013; Liu et al., 2014; Rigamonti et al., 2014).”
BackgroundThe role of macrophages during acute kidney injury: destruction and repair
Han, H. I., Skvarca, L. B., Espiritu, E. B., Davidson, A. J., & Hukriede, N. A. (2018) · Pediatric Nephrology · doi:10.1007/s00467-017-3883-1 · Cited by 124
“Upon activation, the recruited macrophages secrete inflammatory cytokines such as IL-1β, TNFα, IL-12, IL-18, and IL-23 [2] (Fig.”
IL-33 improves wound healing through enhanced M2 macrophage polarization in diabetic mice
He, R., Yin, H., Yuan, B., Liu, T., Luo, L., Huang, P., Dai, L., & Zeng, K. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.06.249 · Cited by 121
“…in all stages of wound healing and orchestrate the wound repair process by exerting proinflammatory functions during the early stage and stimulating proliferation of fibroblasts, keratinocytes, and endothelial cells in the proliferative stage (Brancato and Albina, 2011; Novak and Koh, 2013).”
BackgroundThe M2a macrophage subset may be critically involved in the fibrogenesis of endometriosis in mice
Duan, J., Liu, X., Wang, H., & Guo, S.-W. (2018) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2018.05.017 · Cited by 121
Macrophages in organ fibrosis: from pathogenesis to therapeutic targets
Jiang, Y., Cai, R., Huang, Y., Zhu, L., Xiao, L., Wang, C., & Wang, L. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02247-1 · Cited by 151
Extracellular traps and macrophages: new roles for the versatile phagocyte
Boe, D. M., Curtis, B. J., Chen, M. M., Ippolito, J. A., & Kovacs, E. J. (2015) · Journal of Leukocyte Biology · doi:10.1189/jlb.4ri1014-521r · Cited by 125
“[103–108]), it is not surprising that they are being included in”
BackgroundSousa, A. B., Águas, A. P., Barbosa, M. A., & Barbosa, J. N. (2022) · Regenerative Biomaterials · doi:10.1093/rb/rbac065 · Cited by 123
“It is described in the literature that about 85% of macrophages in the wounded tissue have an M1 pro-inflammatory phenotype in the early stages of repair, and a switch is observed by Days 5–7 to about 80–85% of anti-inflammatory M2 macrophages [37].”
BackgroundAdaptive Immunity to FungiPreprint
Verma, A. H., Wüthrich, M. D., Deepe, G. S., & Klein, B. S. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019612 · Cited by 123
Distinct inflammatory and wound healing responses to complex caudal fin injuries of larval zebrafish
Miskolci, V., Squirrell, J. M., Rindy, J., Vincent, W. J. B., Sauer, J., Gibson, A. L. F., Eliceiri, K. W., & Anna Huttenlocher, A. (2019) · eLife · doi:10.7554/elife.45976 · Cited by 114
3D in vitro M2 macrophage model to mimic modulation of tissue repair
Sapudom, J., Karaman, S., Mohamed, W. K. E. A., Garcia‐Sabaté, A., Quartey, B. C., & Teo, J. C. M. (2021) · npj Regenerative Medicine · doi:10.1038/s41536-021-00193-5 · Cited by 120
Giant cells around bone biomaterials: Osteoclasts or multi-nucleated giant cells?
Miron, R. J., Zohdi, H., Fujioka‐Kobayashi, M., & Bosshardt, D. D. (2016) · Acta Biomaterialia · doi:10.1016/j.actbio.2016.09.029 · Cited by 113
Temporal changes in macrophage phenotype after peripheral nerve injury
Tomlinson, J. E., Žygelytė, E., Grenier, J. K., Edwards, M. G., & Cheetham, J. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1219-0 · Cited by 112
Ayaub, E. A., Kolb, P. S., Mohammed‐Ali, Z., Tat, V., Murphy, J. S., Bellaye, P., Shimbori, C., Boivin, F. J., Lai, R., Lynn, E. G., et al. (2016) · The Journal of Pathology · doi:10.1002/path.4738 · Cited by 116
“To further characterize the macrophage polarization pattern in this system, we performed immunohistochemical staining of arginase-1 and mannose receptor 1 (MR1) as markers of pro-fibrotic M2 macrophages [33,34].”
MethodEffect of Platelet-Rich Plasma on M1/M2 Macrophage Polarization
Uchiyama, R., Toyoda, E., Maehara, M., Wasai, S., Omura, H., Watanabe, M., & Sato, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22052336 · Cited by 115
“and are essential for early tissue repair of damaged or inflamed areas [30,31].”
BackgroundBiomaterials strategies to balance inflammation and tenogenesis for tendon repair
Hou, J., Yang, R., Vuong, I., Li, F., Kong, J., & Mao, H. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.05.043 · Cited by 112
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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