Macrophage phenotypes in the collagen-induced foreign body reaction in rats

Putten, Sander M. van; Ploeger, Diana; Popa, Eliane R.; Bank, Ruud A.

doi:10.1016/j.actbio.2013.01.022

Cited by 76 publications

(60 citation statements)

References 36 publications

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“…Taken together, it seems clear that there is a substantial proportion of macrophages that ED1 does not label. Even allowing for a small amount of overlap between the two subpopulations, defining all macrophages using ED1 and ignoring the substantial unlabelled ED1-population [Keane et al, 2012;van Putten et al, 2013] or using ED1+ cells as a basis for calculating M1 and M2 macrophage fractions [Badylak et al, 2008;Brown et al, 2009] is clearly problematic.…”

Section: Discussionmentioning

confidence: 99%

“…Although M2 and alternative terms have often been used interchangeably, it has been well argued [Gordon, 2003;Stout, 2010] that the latter should be reserved for the M2a subset as coined by Stein et al [1992] to describe the IL-4-driven phenotype, and we will use this nomenclature here. 'M2 markers' in rat in vivo studies have included CD163, arginase-1 and mannose receptor (MR)/ CD206 [Badylak et al, 2008;Brown et al, 2009;Mueller and Schultze-Mosgau, 2011;Ahn et al, 2012;Brown et al, 2012a;Keane et al, 2012;van Putten et al, 2013]. It is widely acknowledged that although the M1/M2 distinction provides a useful conceptual framework for macrophage polarisation [Mantovani et al, 2004], segregation of phenotypes into two distinct subcategories is a major oversimplification [Brown et al, 2012b].…”

Section: Introductionmentioning

confidence: 99%

“…M1 macrophages, also designated as pro-inflammatory, or 'classically activated', are well-defined and characterised, and have been labelled in the rat using markers such as CD80, CCR7 and inducible nitric oxide synthase (iNOS) [Badylak et al, 2008;Brown et al, 2009;Mueller and Schultze-Mosgau, 2011;Brown et al, 2012a;Keane et al, 2012;van Putten et al, 2013]. The classification and characterisation of M2, or non-classically activated macrophages, on the other hand is still evolving.…”

Section: Introductionmentioning

confidence: 99%

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Macrophage Phenotype in Response to Implanted Synthetic Scaffolds: An Immunohistochemical Study in the Rat

Palmer

Abberton

Mitchell

et al. 2014

Cells Tissues Organs

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Macrophages predominate among the cells that directly interact with biomaterials and are key orchestrators of host-biomaterial interactions. However, the macrophage response to synthetic scaffolds in particular has not been well studied. The aim of this study was therefore to characterise the macrophage response to several synthetic scaffolds in the rat using immunohistological techniques for a panel of markers of macrophage subclass or activation, including ED1 (CD68), ED2 (CD163), CD80, mannose receptor and inducible nitric oxide synthase (iNOS). Materials were implanted subcutaneously and collected after 6-8 weeks during the chronic phase of the host response. Unmodified polycaprolactone scaffolds uniquely demonstrated a total lack of both macrophage adherence to surfaces and a wider foreign body response compared to scaffolds composed of poly(lactic-co-glycolic acid) (PLGA) and polyurethanes (PURs), with those macrophages present having a clear M2 (MR+, CD80-, iNOS-) phenotype. PLGA scaffolds displayed an M1-dominant (CD80+, iNOS+, MR-) response with substantial foreign body giant cell (FBGC) formation, whilst PUR scaffold FBGCs had a more mixed M1 (CD80+, iNOS+) and M2 (MR+) phenotype. The study also identified that the use of the ED1 antibody in the rat as a pan-macrophage marker is problematic as there is a separate and substantial ED2-positive macrophage population that it does not label, both in response to biomaterials and in normal tissues. The biomaterial-dependent nature of activation for both macrophages and FBGCs was confirmed, and nuanced M1/M2 phenotypes were described.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Macrophage Phenotype in Response to Implanted Synthetic Scaffolds: An Immunohistochemical Study in the Rat

Palmer

Abberton

Mitchell

et al. 2014

Cells Tissues Organs

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“…While both dexamethasone and anti-VEGF treatment delayed cell migration and vessel dilation at this early phase, these effects had subsided in the anti-VEGF group by day 2. At day 2, in dexamethasone-treated corneas, limbal vessels continued to resist dilation, and accumulation of mature macrophages at the suture site was suppressed despite an increased number of infiltrating myeloid cells (macrophages likely collect at the suture in an attempt to digest foreign material (van Putten et al, 2013), but even play a role in producing VEGF and other cytokines (Lu et al, 2008). Interestingly, these two parameters in the pre-sprouting phase at day 2 appeared to correlate with final neovascular invasion at day 7, while the early migration of inflammatory myeloid cells and total myeloid cell presence did not appear to relate to the final development of neovessels.…”

Section: Discussionmentioning

confidence: 99%

Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model

Mirabelli

Peebo

Xeroudaki

et al. 2014

Experimental Eye Research

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Inflammatory angiogenesis is the pathogenic mechanism of various sight-threatening eye diseases, among them corneal neovascularization. Current treatment options include steroids which have undesirable side effects, or anti-VEGF which has only limited efficacy. In an inflammatory environment, however, angiogenesis can be stimulated by numerous factors not directly targeted by anti-VEGF therapy. The aim of this study was to induce corneal inflammation leading to angiogenesis, and investigate the early, differential effects of steroid and anti-VEGF therapy at the cellular, tissue, and gene expression levels. Fifty-two Wistar rats received a single intrastromal corneal suture to induce a controlled inflammatory angiogenic response. Rats were subsequently treated with dexamethasone, rat specific anti-VEGF, or goat IgG (control), topically 4 times daily for 7 days. In vivo confocal microscopy of the cornea was performed longitudinally from 5 h up to 7 d to investigate morphology at the cellular and tissue-level. In vivo photographic vessel analysis and immunohistochemistry were also performed. RT-PCR for VEGF-A, FGF-2, IL-6, TNF-alpha, CXCL2, CCL2, CCL3 and DLL4 was performed at 24 h, and for VEGF-A, IL-6, TNF-alpha, FGF-2, CXCL2, CCL2, and CCL3 at 7 days. Early infiltration of CD11b + myeloid cells into the cornea at 5 h post-suture was delayed by both treatments relative to controls; however neither treatment was able to suppress accumulation of myeloid cells at day 2 or 7. Limbal vessel dilation was inhibited at 5 h by both treatments, but only dexamethasone showed sustained effect until day 2. Early macrophage recruitment was also suppressed by dexamethasone (but not by anti-VEGF) until day 2. Dexamethasone furthermore suppressed corneal neovascularization at day 7 by over 90%, whereas suppression by anti-VEGF was 14%. Despite differential suppression of vessel dilation, macrophage recruitment, and vascular invasion, anti-VEGF and dexamethasone both down-regulated VEGF-A and IL-6 expression at 24 h with sustained effect to 7 d. They also both down regulated FGF-2 and TNF-alpha at 24 h and CCL2 at 7 d. In conclusion, anti-angiogenic treatments influence early, pre-angiogenic tissue activity such as limbal vessel dilation, inflammatory cell infiltration of the stroma, and macrophage recruitment. Importantly, the differential effects of steroids and anti-VEGF treatment in suppressing neovascular growth could not be attributed to differential inhibition of several major angiogenic and inflammatory factors in the early pre-sprouting phase, including IL-6, VEGF-A, FGF-2, TNF-alpha, CCL2, CCL3, CXCL2, or DLL4.

Funding Agencies|Crown Princess Margaretas Foundation; County Council of Ostergotland; Swedish Research Council [2012-2472]

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“…Trying to 36 overcome these issues, this work proposes the combination of poly(3-hydroxybutyrate-co-hydroxyvaler- 37 ate) (PHBV) structures with adipose-derived stem cells (ASCs) to offer biomechanical and biochemical 38 signaling cues necessary to improve wound healing in a full-thickness model. PHBV scaffold maintained 39 the wound moisture and demonstrated enough mechanical properties to withstand wound contraction.…”

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confidence: 99%

Polyhydroxybutyrate-co-hydroxyvalerate structures loaded with adipose stem cells promote skin healing with reduced scarring

et al. 2015

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Macrophage phenotypes in the collagen-induced foreign body reaction in rats

Cited by 76 publications

References 36 publications

Macrophage Phenotype in Response to Implanted Synthetic Scaffolds: An Immunohistochemical Study in the Rat

Macrophage Phenotype in Response to Implanted Synthetic Scaffolds: An Immunohistochemical Study in the Rat

Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model

Polyhydroxybutyrate-co-hydroxyvalerate structures loaded with adipose stem cells promote skin healing with reduced scarring

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