A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow 119991, Russia.
Physical Department, Lomonosov Moscow State University, Moscow 119991, Russia.
Mediators Inflamm. 2018 Feb 14;2018:1574928. doi: 10.1155/2018/1574928. eCollection 2018.
In patients with reperfusion after ischemia and early development of diabetes, neutrophils can attach to blood vessel walls and release their aggressive bactericide agents, which damage the vascular walls. Insulin and 17-estradiol (E2) relieve the vascular complications observed in metabolic disorders. In contrast, glucagon plays an essential role in the pathophysiology of diabetes. We studied the effect of hormones on neutrophil secretion during adhesion to fibronectin. Amino acid analysis revealed that proteins secreted by neutrophils are characterized by a stable amino acid profile enriched with glutamate, leucine, lysine, and arginine. The total amount of secreted proteins defined as the sum of detected amino acids was increased in the presence of insulin and reduced in the presence of glucagon. E2 did not affect the amount of protein secretion. Proteome analysis showed that in the presence of insulin and E2, neutrophils secreted metalloproteinases MMP-9 and MMP-8 playing a key role in modulation of the extracellular matrix. In contrast, glucagon induced the secretion of cathepsin G, a key bactericide protease of neutrophils. Cathepsin G can promote the development of vascular complications because of its proinflammatory activity and ability to stimulate neutrophil adhesion via the proteolysis of surface receptors.
在缺血后再灌注和早期发生糖尿病的患者中，中性粒细胞可以附着在血管壁上并释放其具有侵袭性的杀菌剂，从而损伤血管壁。胰岛素和 17-雌二醇（E2）可缓解代谢紊乱中观察到的血管并发症。相比之下，胰高血糖素在糖尿病的病理生理学中发挥着重要作用。我们研究了激素对中性粒细胞在附着于纤维连接蛋白时分泌的影响。氨基酸分析表明，中性粒细胞分泌的蛋白质的特征是富含谷氨酸、亮氨酸、赖氨酸和精氨酸的稳定氨基酸谱。在存在胰岛素和降低的情况下，存在于分泌蛋白的量定义为检测到的氨基酸的总和增加。E2 不影响蛋白质分泌的量。蛋白质组分析表明，在胰岛素和 E2 的存在下，中性粒细胞分泌金属蛋白酶 MMP-9 和 MMP-8，它们在细胞外基质的调节中起关键作用。相比之下，胰高血糖素诱导中性粒细胞杀菌蛋白酶组织蛋白酶 G 的分泌。组织蛋白酶 G 可以通过表面受体的蛋白水解促进血管并发症的发展，因为它具有促炎活性和刺激中性粒细胞黏附的能力。
