Hyperbaric Oxygen Inhibits Reperfusion-Induced Neutrophil Polarization and Adhesion Via Plasmin-Mediated VEGF Release
Plastic and Reconstructive Surgery - Global Open
Background: Ischemia-reperfusion (IR) injury is seen in many settings such as free flap salvage and limb replantation/revascularization. The consequences - partial/total flap loss, functional muscle loss, or amputation - can be devastating. Of the treatment options available for IR injury, hyperbaric oxygen (HBO) is the most beneficial. HBO inhibits neutrophil-endothelial adhesion through interference of CD18 neutrophil polarization in IR, a process mediated by nitric oxide. The purposes of this study were to examine the involvement of vascular endothelial growth factor (VEGF) in the beneficial HBO effect on CD18 polarization and neutrophil adhesion and investigate the effect of plasmin on VEGF expression in skeletal muscle following IR injury. Methods: A rat gracilis muscle model of IR injury was used to evaluate the effect of VEGF in IR, with and without HBO, on neutrophil CD18 polarization and adhesion in vivo and ex vivo. Furthermore, we investigated the effects that plasmin has on VEGF expression in gracilis muscle and pulmonary tissue by blocking its activation with alpha-2-antiplasmin. Results: HBO treatment following IR injury significantly decreased neutrophil polarization and adhesion ex vivo compared with the IR group. Anti-VEGF reversed the beneficial HBO effect after IR with polarization and adhesion. In vivo adhesion was also increased by anti-VEGF. HBO treatment of IR significantly increased the VEGF protein in both gracilis and pulmonary vasculature. Alpha-2-antiplasmin significantly reversed the HBO-induced increase of VEGF in gracilis muscle. Conclusions: These results suggest that HBO inhibits CD18 polarization and neutrophil adhesion in IR injury through a VEGF-mediated pathway involving the extracellular matrix plasminogen system. © 2017 The Authors.
Kleban, S. R.,
Stephenson, L. L.,
Murphy, P. S.,
Letourneau, P. R.,
Fang, X. H.,
Wang, W. Z.,
Baynosa, R. C.
Hyperbaric Oxygen Inhibits Reperfusion-Induced Neutrophil Polarization and Adhesion Via Plasmin-Mediated VEGF Release.
Plastic and Reconstructive Surgery - Global Open, 5(9),