scholarly journals Regulation of Macrophage Polarization and Wound Healing

2012 ◽  
Vol 1 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Christopher J. Ferrante ◽  
Samuel Joseph Leibovich
Keyword(s):  
Wound Healing ◽  
Macrophage Polarization

scholarly journals Inflammatory M1-like macrophages polarized by NK-4 undergo enhanced phenotypic switching to an anti-inflammatory M2-like phenotype upon co-culture with apoptotic cells

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Keizo Kohno ◽  
Satomi Koya-Miyata ◽  
Akira Harashima ◽  
Takahiko Tsukuda ◽  
Masataka Katakami ◽  
...  
Keyword(s):  
Wound Healing ◽  
Chronic Wounds ◽  
Macrophage Polarization ◽  
Phenotypic Switching ◽  
Apoptotic Cells ◽  
Phenotypic Switch ◽  
Inflammatory Phase ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Anti Inflammatory

Abstract Background NK-4 has been used to promote wound healing since the early-1950s; however, the mechanism of action of NK-4 is unknown. In this study, we examined whether NK-4 exerts a regulatory effect on macrophages, which play multiple roles during wound healing from the initial inflammatory phase until the tissue regeneration phase. Results NK-4 treatment of THP-1 macrophages induced morphological features characteristic of classically-activated M1 macrophages, an inflammatory cytokine profile, and increased expression of the M1 macrophage-associated molecules CD38 and CD86. Interestingly, NK-4 augmented TNF-α production by THP-1 macrophages in combination with LPS, Pam3CSK4, or poly(I:C). Furthermore, NK-4 treatment enhanced THP-1 macrophage phagocytosis of latex beads. These results indicate that NK-4 drives macrophage polarization toward an inflammatory M1-like phenotype with increased phagocytic activity. Efferocytosis is a crucial event for resolution of the inflammatory phase in wound healing. NK-4-treated THP-1 macrophages co-cultured with apoptotic Jurkat E6.1 (Apo-J) cells switched from an M1-like phenotype to an M2-like phenotype, as seen in the inverted ratio of TNF-α to IL-10 produced in response to LPS. We identified two separate mechanisms that are involved in this phenotypic switch. First, recognition of phosphatidylserine molecules on Apo-J cells by THP-1 macrophages downregulates TNF-α production. Second, phagocytosis of Apo-J cells by THP-1 macrophages and activation of PI3K/Akt signaling pathway upregulates IL-10 production. Conclusion It is postulated that the phenotypic switch from a proinflammatory M1-like phenotype to an anti-inflammatory M2-like phenotype is dysregulated due to impaired efferocytosis of apoptotic neutrophils at the wound site. Our results demonstrate that NK-4 improves phagocytosis of apoptotic cells, suggesting its potential as a therapeutic strategy to resolve sustained inflammation in chronic wounds.

Bioinspired Nanofibrous Glycopeptide Hydrogel Dressing for Accelerating Wound Healing: A Cytokine‐Free, M2‐Type Macrophage Polarization Approach

2020 ◽  
Vol 30 (52) ◽  
pp. 2006454
Author(s):  
Zujian Feng ◽  
Qi Su ◽  
Chuangnian Zhang ◽  
Pingsheng Huang ◽  
Huijuan Song ◽  
...  
Keyword(s):  
Wound Healing ◽  
Macrophage Polarization

scholarly journals Abnormal Cell Responses and Role of TNF-αin Impaired Diabetic Wound Healing

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Fanxing Xu ◽  
Chenying Zhang ◽  
Dana T. Graves
Keyword(s):  
Wound Healing ◽  
Macrophage Polarization ◽  
Diabetic Wound ◽  
Major Health Problem ◽  
Abnormal Cell ◽  
Fibroblast Migration ◽  
Cell Responses ◽  
Impaired Healing ◽  
Diabetic Wound Healing

Impaired diabetic wound healing constitutes a major health problem. The impaired healing is caused by complex factors such as abnormal keratinocyte and fibroblast migration, proliferation, differentiation, and apoptosis, abnormal macrophage polarization, impaired recruitment of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs), and decreased vascularization. Diabetes-enhanced and prolonged expression of TNF-αalso contributes to impaired healing. In this paper, we discuss the abnormal cell responses in diabetic wound healing and the contribution of TNF-α.

Macrophage polarization in wound healing: role of aloe vera/chitosan nanohydrogel

2019 ◽  
Vol 9 (6) ◽  
pp. 1027-1042 ◽  
Author(s):  
Fatemeh Ashouri ◽  
Fatemeh Beyranvand ◽  
Nasim Beigi Boroujeni ◽  
Majid Tavafi ◽  
Ali Sheikhian ◽  
...  
Keyword(s):  
Wound Healing ◽  
Macrophage Polarization ◽  
Aloe Vera

Development and Characterization of Squalene-Loaded Topical Agar-Based Emulgel Scaffold: Wound Healing Potential in Full-Thickness Burn Model

2020 ◽  
pp. 153473462092162
Author(s):  
T. S. Shanmugarajan ◽  
N. Kalai Selvan ◽  
Varuna Naga Venkata Arjun Uppuluri
Keyword(s):  
Wound Healing ◽  
Tissue Regeneration ◽  
Macrophage Polarization ◽  
Negative Control ◽  
Skin Tissue ◽  
Self Healing ◽  
Full Thickness ◽  
Burn Wound ◽  
Burn Wound Healing ◽  
Tissue Defects

Full-thickness burns pose a major challenge for clinicians to handle because of their restricted self-healing ability. Even though several approaches have been implemented for repairing these burnt skin tissue defects, all of them had unsatisfactory outcomes. Moreover, during recent years, skin tissue engineering techniques have emerged as a promising approach to improve skin tissue regeneration and overcome the shortcomings of the traditional approaches. Although previous literatures report the wound healing effects of the squalene oil, in the current study, for the first time, we developed a squalene-loaded emulgel-based scaffold as a novel approach for potential skin regeneration. This squalene-loaded agar-based emulgel scaffold was fabricated by using physical cross-linking technique using lecithin as an emulsifier. Characterization studies such as X-ray diffraction, Fourier-transform infrared spectroscopy, and field emission scanning electron microscopy revealed the amorphous nature, chemical interactions, and cross-linked capabilities of the developed emulgel scaffold. The squalene-loaded emulgel scaffold showed excellent wound contraction when compared with the agar gel and negative control. In case of the histopathology and recent immunohistochemistry findings, it was clearly evidenced that squalene-loaded emulgel promoted faster rate of the revascularization and macrophage polarization in order to enhance the burn wound healing. Moreover, the findings also revealed that the incorporation of squalene oil into the formulation enhances collagen deposition and accelerates the burnt skin tissue regeneration process. Finally, we conclude that the squalene-loaded emulgel scaffold could be an effective formulation used in the treatment of the burnt skin tissue defects.

scholarly journals The Vitamin D Receptor Regulates Tissue Resident Macrophage Response to Injury

Endocrinology ◽  
2016 ◽  
Vol 157 (10) ◽  
pp. 4066-4075 ◽  
Author(s):  
Lige Song ◽  
Garyfallia Papaioannou ◽  
Hengguang Zhao ◽  
Hilary F. Luderer ◽  
Christine Miller ◽  
...  
Keyword(s):  
Vitamin D ◽  
Wound Healing ◽  
Vitamin D Receptor ◽  
Macrophage Polarization ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Wild Type ◽  
Macrophage Response ◽  
Protein Levels ◽  
Inflammatory Phase

Ligand-dependent actions of the vitamin D receptor (VDR) play a pleiotropic role in the regulation of innate and adaptive immunity. The liganded VDR is required for recruitment of macrophages during the inflammatory phase of cutaneous wound healing. Although the number of macrophages in the granulation tissue 2 days after wounding is markedly reduced in VDR knockout (KO) compared with wild-type mice, VDR ablation does not alter macrophage polarization. Parabiosis studies demonstrate that circulatory chimerism with wild-type mice is unable to rescue the macrophage defect in the wounds of VDR KO mice and reveal that wound macrophages are of local origin, regardless of VDR status. Wound cytokine analyses demonstrated a decrease in macrophage colony-stimulating factor (M-CSF) protein levels in VDR KO mice. Consistent with this, induction of M-CSF gene expression by TGFβ and 1,25-dihydroxyvitamin D was impaired in dermal fibroblasts isolated from VDR KO mice. Because M-CSF is important for macrophage self-renewal, studies were performed to evaluate the response of tissue resident macrophages to this cytokine. A decrease in M-CSF induced proliferation and cyclin D1 expression was observed in peritoneal resident macrophages isolated from VDR KO mice, suggesting an intrinsic macrophage abnormality. Consistent with this, wound-healing assays in mice with macrophage-specific VDR ablation demonstrate that a normal wound microenvironment cannot compensate for the absence of the VDR in macrophages and thus confirm a critical role for the macrophage VDR in the inflammatory response to injury.

scholarly journals Macrophage Polarization Is Impaired in Hemophilia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2499-2499
Author(s):  
Lynn M Knowles ◽  
Daniela Lessig ◽  
Martin Bernard ◽  
Eva C Schwarz ◽  
Hermann Eichler ◽  
...  
Keyword(s):  
Wound Healing ◽  
Blood Cell ◽  
Factor Viii ◽  
Tissue Regeneration ◽  
Red Blood Cell ◽  
Blood Donors ◽  
Macrophage Polarization ◽  
Down Regulation ◽  
Macrophage Differentiation ◽  
Gm Csf

Abstract Macrophages are master regulators of inflammation and wound healing. As such they play an important role in hemophilia, which is commonly associated with delayed tissue regeneration and bleeding-induced joint inflammation. The objective of this study is to determine if macrophage function is deregulated in hemophilia and whether this affects the physiological balance of tissue regeneration and inflammation. For this study, we analyzed monocytes and plasma from a cohort of 26 adult patients with hemophilia A or B that visited our clinic for their annual routine check-up. Patients with acute bleeding events were excluded. The majority of patients had severe forms of hemophilia with factor VIII or IX activity < 1% and, therefore, received prophylactic factor replacement therapy (recombinant or plasmatic) but we also included patients with moderate to mild hemophilia, which were only treated in case of bleeding. Corresponding control samples stemmed from healthy male individuals that we recruited randomly from our blood donor center. To assess macrophage differentiation, we isolated monocytes from the peripheral blood of hemophilia patients as well as healthy controls and began treatment with M-CSF or GM-CSF for 7 days. Macrophage differentiation was confirmed by phase contrast and fluorescence microscopy, which revealed a spread and elongated cell phenotype in donor monocytes in the presence of M-CSF and, to a lesser extent, GM-CSF. Hemophilia monocytes, on the other hand, failed to spread properly in response to either of the cytokines suggesting that macrophage polarization is diminished in patients with reduced activity of coagulation factor VIII or IX. As hemophilia macrophages failed to spread in response to M-CSF, they also failed to express TNFα and CD163, which are macrophage differentiation markers typically induced by M-CSF. In contrast, GM-CSF-induced differentiation was only mildly suppressed suggesting that hemophilia macrophages specifically resist the differentiating stimulus of M-CSF. Consequently, we experienced a significant impairment in M-CSF-induced regenerative macrophage functions such as clot infiltration and red blood cell phagocytosis in hemophilia. Intriguingly, while monocyte invasion was impaired, protein expression in response to M-CSF was regained with respect to CD163 and CD206 after embedding hemophilia monocytes in clotted plasma from healthy blood donors suggesting that a functioning coagulation system has positive effects on regenerative macrophage functions. The inability of hemophilia macrophages to promote M-CSF-mediated signals correlates with a marked down regulation of the M-CSF receptor CSF-1R on hemophilia monocytes as determined in citrated whole blood by flow cytometry. Alongside with a modest reduction of GM-CSF-R, we also detected a substantial reduction of CD163 and Tie2, which are specifically expressed on regenerative monocytes/macrophages, suggesting that clotting deficiencies impair the immune function either directly or indirectly. To further analyze the immune status of hemophilia patients, we performed a cytokine array on plasma samples from hemophiliacs versus healthy blood donors, which revealed the down regulation of a large spectrum of anti-inflammatory and regenerative cytokines in the blood of hemophilia patients. Among the few cytokines upregulated in the blood of hemophiliacs, the adipokine leptin was the most prominent (6-fold, hemophiliac vs. donor). Since leptin has been shown to cause deregulation of the innate immunity, we treated the human monocyte cell line THP1 with recombinant leptin and found a significant inhibitory effect of M-CSF-induced spreading and clot invasion. Therefore, these data suggest that high leptin levels in the blood can reiterate the changes in monocyte function we observed in hemophilia. Together, we conclude that macrophage differentiation is deregulated in hemophilia as a result of resistance towards the cytokine M-CSF. Consequently, hemophilia macrophages are unable to properly perform regenerative functions such as clot invasion and red blood cell phagocytosis. The hemophilic monocyte/macrophage phenotype we describe can be induced by high levels of leptin and mitigated by correcting the clotting dysfunction suggesting a two prone approach to prevent delayed wound healing and persistent inflammation in hemophilia. Disclosures No relevant conflicts of interest to declare.

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