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

Abstract

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.

Survey of Molecular Mechanisms of Hyperbaric Oxygen in Tissue Repair

“…In a prospective randomized trial with 32 patients suffering from diabetic foot ulcers, supportive HBO was able to promote wound healing by stimulating angiogenesis, decreasing inflammation, and increasing the nitrite levels [ 5 ]. Similar results were obtained in another clinical study which proved the anti-inflammatory efficacy of HBO in patients with chronic diabetic wounds [ 6 ]. Moreover, in a prospective clinical trial involving 27 patients with diabetic food ulcers, adjunctive HBO resulted in accelerated wound healing by stimulating the vascular endothelial growth factor and the epidermal growth factor [ 7 ].…”

Diabetic Wound-Healing Science

“…In a small study with 17 patients, hyperbaric oxygen therapy was noted to induce cytoplasmic translocation of HIF-1a and nuclear factor (NF)-kB localization as well as increased VEGF, IL-6, insulin-like growth factor binding protein 3, adiponectin, fibrosis, and angiogenesis while decreasing interferon (IFN)-γ levels [ 148 ]. In addition, the prolonged use of hyperbaric oxygen therapy has also been shown to decrease the recruitment and adhesion of neutrophils, increase oxygen dispersion to damaged tissues, reduce inflammation, and accelerate healing in patients with diabetic ulcers [ 149 , 150 , 151 ]. More recently, studies of topical oxygen therapy rather than HBOT have been shown to promote healing in DFUs and promote an aerobic wound microbiome [ 152 , 153 ].…”

Use of hyperbaric oxygen therapy in the treatment of osteoradionecrosis of the maxilla in patients with head and neck cancer

“…Wound healing is a complex and tightly structured process that requires a well-orchestrated interaction of molecular and cellular events, in which it is divided into several stages, among them: hemostasis, inflammation, re-epithelialization, and tissue remodeling. The activation of the immune system is also part of this stage, acting directly to remove dead cells and matrix debris from the damaged tissue (Baiula et al, 2020).…”