The primary immune response against Staphylococcus aureus is mediated by neutrophils. In response to S. aureus and its proteins, neutrophil shows two different kinds of NETosis, viz. suicidal and vesicular NETosis. Glucose is the major energy source of neutrophils for performing NETosis. However, NETosis was found altered in response to high glucose levels. Growth of S. aureus was also found modulated in response to high glucose and they behave differently at different glucose levels. This work was attempted to study NET release in response to S. aureus cell-free culture supernatant at different glucose concentrations. Freshly isolated neutrophils were treated with different concentrations of glucose along with S. aureus cell-free culture supernatant and were analyzed for neutrophil extracellular trap formation, ROS production, and peptidylarginine deiminase 4 activities. Influence of calcium on NETosis was analyzed using calcium chelator (EDTA) and calcium inhibitor (TMB-8).

With increasing glucose levels, NET release in response to S. aureus cell-free culture supernatant was increased. Oxidant level was also increased dose-dependently with increasing concentrations of glucose. At very high glucose concentrations (> 15 mM), vesicular NETosis was predominantly observed. At these glucose concentrations, peptidylarginine deiminase activity was found to be decreased. Furthermore, calcium quenching in the medium facilitated vesicular mode of NET release.

In conclusion, calcium depletion occurring at high glucose concentrations can reduce peptidylarginine deiminase 4 activity and can thereby promote the vesicular NET release.

中性粒细胞介导了针对金黄色葡萄球菌的主要免疫反应。中性粒细胞对金黄色葡萄球菌及其蛋白有反应，显示出两种不同的NETosis，即。自杀和水泡性netosis。葡萄糖是中性粒细胞进行NETosis的主要能源。然而，发现NETosis响应于高葡萄糖水平而改变。还发现金黄色葡萄球菌的生长响应高葡萄糖而受到调节，并且它们在不同的葡萄糖水平下表现不同。尝试研究这项工作以研究在不同葡萄糖浓度下响应金黄色葡萄球菌无细胞培养上清液的NET释放。新鲜分离的嗜中性粒细胞用不同浓度的葡萄糖和金黄色葡萄球菌处理无细胞培养上清液，并分析中性粒细胞胞外陷阱的形成，ROS的产生和肽酰精氨酸脱亚氨酶4的活性。使用钙螯合剂（EDTA）和钙抑制剂（TMB-8）分析了钙对NETosis的影响。

随着葡萄糖水平的增加，响应于金黄色葡萄球菌无细胞培养物上清液的NET释放增加。氧化剂水平也随着葡萄糖浓度的增加而剂量依赖性地增加。在很高的葡萄糖浓度（> 15 mM）下，主要观察到水泡性NETosis。在这些葡萄糖浓度下，发现肽酰精氨酸脱亚氨酶活性降低。此外，在培养基中的钙淬灭促进了NET释放的囊泡模式。

总之，在高葡萄糖浓度下发生的钙耗竭可降低肽基精氨酸脱亚氨酶4的活性，从而促进水泡网的释放。