Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Department of Plastic and Reconstructive Surgery, Soroka University Medical Center, Beer-Sheva 8410101, Israel.
Int J Mol Sci. 2022 Jul 1;23(13):7364. doi: 10.3390/ijms23137364.
Wound healing requires a non-compromising combination of inflammatory and anti-inflammatory 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 enzymes, 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 (hAAT) and protease-inhibition-lacking hAAT (hAAT). The impact of both hAAT forms was determined by an epithelial cell gap closure assay, and by excisional skin injuries via a microemulsion 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, particularly at early time points. Unlike dexamethasone-treated wounds, both resulted in closed borders at the 8-h time point. In untreated and hAAT-treated wounds, leukocytic infiltrates were widespread, in hAAT-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.
伤口愈合需要炎症和抗炎过程的非妥协组合。人α1-抗胰蛋白酶（hAAT）是一种循环糖蛋白，在急性反应期间和健康妊娠期间升高，具有组织保护和诱导耐受作用；尽管具有抗炎作用，但 hAAT 增强了再血管化。hAAT 阻断组织降解酶，包括中性粒细胞弹性蛋白酶；因此，尚不清楚在 hAAT 丰富的条件下伤口愈合如何改善。在这里，通过上皮细胞间隙闭合测定和通过优化用于开放性伤口的微乳液来检查存在重组 hAAT（hAAT）和缺乏蛋白酶抑制的 hAAT（hAAT）的伤口愈合。通过上皮细胞间隙闭合测定和通过优化用于开放性伤口的微乳液来检查存在重组 hAAT（hAAT）和缺乏蛋白酶抑制的 hAAT（hAAT）的伤口愈合。通过上皮细胞间隙闭合测定和通过优化用于开放性伤口的微乳液来检查存在重组 hAAT（hAAT）和缺乏蛋白酶抑制的 hAAT（hAAT）的伤口愈合。通过上皮细胞间隙闭合测定和通过优化用于开放性伤口的微乳液来检查存在重组 hAAT（hAAT）和缺乏蛋白酶抑制的 hAAT（hAAT）的伤口愈合。两种 hAAT 形式的影响均通过上皮细胞间隙闭合测定和通过微乳液测定来确定，微乳液优化用于开放性伤口。在 8 小时后检查中性粒细胞浸润。结果表明，两种 hAAT 形式均加速了上皮细胞间隙闭合和切伤伤口闭合，尤其是在早期时间点。与地塞米松处理的伤口不同，两种形式均在 8 小时时间点导致闭合边界。在未处理和 hAAT 处理的伤口中，白细胞浸润广泛，在 hAAT 处理的伤口中，白细胞浸润呈节段性，在地塞米松处理的伤口中，白细胞浸润稀少。两种 hAAT 形式均降低了白细胞介素-1β并增加了 VEGF 基因表达。总之，hAAT 可改善上皮细胞迁移并改善体内伤口的结局，而与蛋白酶抑制无关。尽管两种形式的 hAAT 都允许中性粒细胞浸润，但只有天然 hAAT 才能形成离散的中性粒细胞组织簇。
