Bhattacharya Abhisek, Wei Qin, Shin Jin Na, Abdel Fattah Elmoataz, Bonilla Diana L, Xiang Qian, Eissa N Tony
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Cell Rep. 2015 Sep 22;12(11):1731-9. doi: 10.1016/j.celrep.2015.08.019. Epub 2015 Sep 3.
Autophagy, an intracellular degradation and energy recycling mechanism, is emerging as an important regulator of immune responses. However, the role of autophagy in regulating neutrophil functions is not known. We investigated neutrophil biology using myeloid-specific autophagy-deficient mice and found that autophagy deficiency reduced neutrophil degranulation in vitro and in vivo. Mice with autophagy deficiency showed reduced severity of several neutrophil-mediated inflammatory and autoimmune disease models, including PMA-induced ear inflammation, LPS-induced breakdown of blood-brain barrier, and experimental autoimmune encephalomyelitis. NADPH oxidase-mediated reactive oxygen species generation was also reduced in autophagy-deficient neutrophils, and inhibition of NADPH oxidase reduced neutrophil degranulation, suggesting NADPH oxidase to be a player at the intersection of autophagy and degranulation. Overall, this study establishes autophagy as an important regulator of neutrophil functions and neutrophil-mediated inflammation in vivo.
自噬是一种细胞内降解和能量循环机制，正逐渐成为免疫反应的重要调节因子。然而，自噬在调节中性粒细胞功能中的作用尚不清楚。我们使用髓系特异性自噬缺陷小鼠研究了中性粒细胞生物学，发现自噬缺陷在体外和体内均降低了中性粒细胞的脱颗粒作用。自噬缺陷小鼠在几种中性粒细胞介导的炎症和自身免疫性疾病模型中的严重程度降低，包括佛波酯诱导的耳部炎症、脂多糖诱导的血脑屏障破坏以及实验性自身免疫性脑脊髓炎。自噬缺陷的中性粒细胞中烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶介导的活性氧生成也减少，并且抑制NADPH氧化酶可降低中性粒细胞的脱颗粒作用，这表明NADPH氧化酶是自噬和脱颗粒交叉点上的一个参与者。总的来说，这项研究确立了自噬是体内中性粒细胞功能和中性粒细胞介导的炎症的重要调节因子。
