Department of Microbiology and Immunology and the Center for Human Immunology, The University of Western Ontario, London, ON, Canada.
Cell Tissue Res. 2018 Mar;371(3):455-471. doi: 10.1007/s00441-017-2731-8. Epub 2017 Nov 29.
Neutrophils respond nearly instantly to infection, rapidly deploying a potent enzymatic and chemical arsenal immediately upon entering an infected site. This capacity for rapid and potent responses is endowed by stores of antimicrobial proteins contained in readily mobilizable granules. These granules contain the proteins necessary to mediate the recruitment, chemotaxis, antimicrobial function and NET formation of neutrophils. Four granule types exist, and are sequentially deployed as neutrophils enter infected sites. Secretory vesicles are released first, enabling recruitment of neutrophils out of the blood. Next, specific and gelatinase granules are released to enable neutrophil migration and begin the formation of an antimicrobial environment. Finally, azurophilic granules release potent antimicrobial proteins at the site of infection and into phagosomes. The step-wise mobilization of these granules is regulated by calcium signaling, while specific trafficking regulators and membrane fusion complexes ensure the delivery of granules to the correct subcellular site. In this review, we describe neutrophil granules from their formation through to their deployment at the site of infection, focusing on recent developments in our understanding of the signaling pathways and vesicular trafficking mechanisms which mediate neutrophil degranulation.
中性粒细胞几乎能立即对感染做出反应，在进入感染部位后迅速释放出一种有效的酶和化学武器库。这种快速而有效的反应能力源自于储存于易于动员的颗粒中的抗菌蛋白。这些颗粒包含介导中性粒细胞募集、趋化、抗菌功能和 NET 形成所必需的蛋白质。存在四种颗粒类型，它们会随着中性粒细胞进入感染部位而依次释放。首先释放分泌小泡，使中性粒细胞从血液中招募出来。然后，特异性和明胶酶颗粒被释放，使中性粒细胞迁移并开始形成抗菌环境。最后，嗜天青颗粒在感染部位和吞噬体中释放出强效的抗菌蛋白。这些颗粒的逐步动员受钙信号的调节，而特定的运输调节剂和膜融合复合物则确保颗粒递送到正确的亚细胞部位。在这篇综述中，我们描述了中性粒细胞颗粒从形成到在感染部位的释放，重点介绍了我们对介导中性粒细胞脱粒的信号通路和囊泡运输机制的最新理解。
