Accelerated Wound Border Closure Using a Microemulsion Containing Non-Inhibitory Recombinant α1-Antitrypsin

Abstract

Wound healing requires a non-compromising combination of inflammatory and anti-in-flammatory processes. Human α1-antitrypsin (hAAT), a circulating glycoprotein that rises during acute-phase responses and during healthy pregnancies, is tissue-protective and tolerance-inducing; although anti-inflammatory, hAAT enhances revascularization. hAAT blocks tissue-degrading en-zymes, including neutrophil elastase; it is, therefore, unclear how wound healing might improve under hAAT-rich conditions. Here, wound healing was examined in the presence of recombinant hAAT (hAATWT) and protease-inhibition-lacking hAAT (hAATCP). The impact of both hAAT forms was determined by an epithelial cell gap closure assay, and by excisional skin injuries via a micro-emulsion optimized for open wounds. Neutrophilic infiltration was examined after 8 h. According to results, both hAAT forms accelerated epithelial gap closure and excisional wound closure, par-ticularly at early time points. Unlike dexamethasone-treated wounds, both resulted in closed bor-ders at the 8-h time point. In untreated and hAATCP-treated wounds, leukocytic infiltrates were widespread, in hAATWT-treated wounds compartmentalized and in dexamethasone-treated wounds, scarce. Both hAAT forms decreased interleukin-1β and increased VEGF gene expression. In conclusion hAAT improves epithelial cell migration and outcomes of in vivo wounds irrespective of protease inhibition. While both forms of hAAT allow neutrophils to infiltrate, only native hAAT created discrete neutrophilic tissue clusters.