Systemic Delivery of Anti-Integrin αL Antibodies Reduces Early Macrophage Recruitment, Inflammation, and Scar Formation in Murine Burn Wounds

Strudwick, Xanthe L.; Adams, Damian; Pyne, Natasha Theresa; Samuel, Michael S.; Murray, Rachael Z.; Cowin, Allison J.

doi:10.1089/wound.2019.1035

Cited by 15 publications

(15 citation statements)

References 35 publications

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“…Leukocyte integrins are considered as interesting therapeutic targets for the development of new drugs useful to treat inflammatory diseases. In fact, several drugs targeting integrins such as α 4 have proven to be effective for the therapy of Crohn's disease, ulcerative colitis and multiple sclerosis [46,47,65,66] and others are in development to treat ocular diseases [44] or to reduce scar formation [67]. Therefore, further studies on integrin antagonists are necessary to better understand the possibility to develop a combined therapy with HBOT for the treatment of chronic wounds.…”

Section: Plos Onementioning

confidence: 99%

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

et al. 2020

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In recent years, several studies suggested that the ability of hyperbaric oxygen therapy (HBOT) to promote healing in patients with diabetic ulcers and chronic wounds is due to the reduction of inflammatory cytokines and to a significant decrease in neutrophils recruitment to the damaged area. α 4 and β 2 integrins are receptors mediating the neutrophil adhesion to the endothelium and the comprehension of the effects of hyperbaric oxygenation on their expression and functions in neutrophils could be of great importance for the design of novel therapeutic protocols focused on anti-inflammatory agents. In this study, the α 4 and β 2 integrins' expression and functions have been evaluated in human primary neutrophils obtained from patients with chronic non-healing wounds and undergoing a prolonged HBOT (150 kPa per 90 minutes). The effect of a peptidomimetic α 4 β 1 integrin antagonist has been also analyzed under these conditions. A statistically significant decrease (68%) in β 2 integrin expression on neutrophils was observed during the treatment with HBO and maintained one month after the last treatment, while α 4 integrin levels remained unchanged. However, cell adhesion function of both neutrophilic integrins α 4 β 1 and β 2 was significantly reduced 70 and 67%, respectively), but α 4 β 1 integrin was still sensitive to antagonist inhibition in the presence of fibronectin, suggesting that a combined therapy between HBOT and integrin antagonists could have greater antinflammatory efficacy.

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Section: Plos Onementioning

confidence: 99%

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

et al. 2020

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“…As demonstrated in Figure A, F4/80 + macrophages were found to be broadly distributed at and below the surface of the wound bed tissue (white arrows). Samples were additionally costained with iNOS and YM-1 (also known as chitinase-like protein 3/Chil3) as markers of the M1 and M2 phenotypes, respectively (Figure B) . The mean fluorescence intensities of double-positive F4/80 + iNOS and F4/80 + YM-1 macrophages were compared in each section at both wound margins and at the center (Figure C; three fields per section, n = 6 animals per group unless otherwise indicated).…”

Section: Resultsmentioning

confidence: 99%

“…Samples were additionally costained with iNOS and YM-1 (also known as chitinase-like protein 3/Chil3) as markers of the M1 and M2 phenotypes, respectively (Figure 5B). 18 The mean fluorescence intensities of double-positive F4/80 + iNOS and F4/80 + YM-1 macrophages were compared in each section at both wound margins and at the center (Figure 5C; three fields per section, n = 6 animals per group unless otherwise indicated). Comparing the sham and experimental groups, it was found that wounds treated with SDF or lipoSDF in hydrogels expressed a higher ratio of YM-1 + to iNOS + macrophages compared to administering the proteins without hydrogel and that this ratio was significantly higher when compared to the sham control (*p < 0.05).…”

Section: Migration Of Bmdms In Sdf-containing Hydrogelsmentioning

confidence: 99%

Liposomal SDF-1 Alpha Delivery in Nanocomposite Hydrogels Promotes Macrophage Phenotype Changes and Skin Tissue Regeneration

Varrey

Liang

et al. 2021

ACS Biomater. Sci. Eng.

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Skin regeneration in chronic wounds is often delayed due to persistent inflammation induced by underlying conditions such as diabetes. This effect is mediated, in part, by macrophages present in the wound, which can be stimulated to adopt either pro- or anti-inflammatory phenotypes depending on the status of the local microenvironment. In this work, the prohealing chemokine stromal cell-derived factor-1 alpha (SDF-1α) is controllably released from a hydrogel-based biomaterial to promote skin tissue regeneration and wound closure. This innovative nanocomposite hydrogel system releases liposomal stromal cell-derived factor-1 alpha (lipoSDF) as a new treatment approach for dorsal full-thickness skin wounds in wild-type and diabetic mice. Using this strategy, the recruitment and polarization of macrophages primarily of the anti-inflammatory phenotype were observed, along with a decreased amount of open wound surface area in diabetic mice after 28 days. This was accompanied by histological observations of increased epidermal stratification and dermal angiogenesis. These findings represent an important step of investigation distinctive in its field for developing immunomodulatory biomaterials that are able to influence macrophage phenotype and promote healing as hydrogel-based wound dressings.

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“…It could be by the use of biomaterial dressings that might modulate the immune system or through the modulation of the skin's own host defence peptides to clear an infection and alter the inflammatory phase [65][66][67][68][69]. It might be as simple as reducing the number of monocytes/macrophages entering the wound by repurposing of drugs, for example the use of anti-integrin antibodies to reduce the macrophage load [70]. Alternatively, it might be altering the phenotype of the macrophage, reducing the factors such as TNF in the wound with an anti-TNF antibody to reduce inflammation, or the design of new therapies to dampen wound inflammation [51].…”

Section: Discussionmentioning

confidence: 99%

Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds

et al. 2021

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Macrophages play a prominent role in wound healing. In the early stages, they promote inflammation and remove pathogens, wound debris, and cells that have apoptosed. Later in the repair process, they dampen inflammation and secrete factors that regulate the proliferation, differentiation, and migration of keratinocytes, fibroblasts, and endothelial cells, leading to neovascularisation and wound closure. The macrophages that coordinate this repair process are complex: they originate from different sources and have distinct phenotypes with diverse functions that act at various times in the repair process. Macrophages in individuals with diabetes are altered, displaying hyperresponsiveness to inflammatory stimulants and increased secretion of pro-inflammatory cytokines. They also have a reduced ability to phagocytose pathogens and efferocytose cells that have undergone apoptosis. This leads to a reduced capacity to remove pathogens and, as efferocytosis is a trigger for their phenotypic switch, it reduces the number of M2 reparative macrophages in the wound. This can lead to diabetic foot ulcers (DFUs) forming and contributes to their increased risk of not healing and becoming infected, and potentially, amputation. Understanding macrophage dysregulation in DFUs and how these cells might be altered, along with the associated inflammation, will ultimately allow for better therapies that might complement current treatment and increase DFU’s healing rates.

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Systemic Delivery of Anti-Integrin αL Antibodies Reduces Early Macrophage Recruitment, Inflammation, and Scar Formation in Murine Burn Wounds

Cited by 15 publications

References 35 publications

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

Integrin-mediated adhesive properties of neutrophils are reduced by hyperbaric oxygen therapy in patients with chronic non-healing wound

Liposomal SDF-1 Alpha Delivery in Nanocomposite Hydrogels Promotes Macrophage Phenotype Changes and Skin Tissue Regeneration

Skin Wound Healing: Normal Macrophage Function and Macrophage Dysfunction in Diabetic Wounds

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