Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation.
Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation.
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DOI：
10.1111/imr.12452
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发表时间：
2016-09
影响因子：
8.7
通讯作者：
Catz SD
中科院分区：
文献类型：
--
作者：
Ramadass M;Catz SD
中性粒细胞构成了抵御入侵微生物的第一道细胞防线，并调节随后的先天和获得性免疫反应。为了对感染做出快速而准确的反应，中性粒细胞依赖于储存在各种细胞内颗粒中的预先形成的效应分子。中性粒细胞颗粒含有杀菌因子、呼吸爆发氧化酶的膜结合成分、膜结合的黏附分子和促进中性粒细胞所有功能执行的受体，包括黏附、转运、吞噬、脱颗粒和中性粒细胞细胞外陷阱的形成。细胞内细胞器的快速动员受囊泡转运机制的调控，这些机制由效应分子控制，其中包括小的GTP酶及其相互作用的蛋白。在这篇综述中，我们重点介绍了处于中性粒细胞功能调节中心阶段的机械性过程的最新发现，强调了由运输调节器控制的离散的和选择性的途径。特别是，我们描述了由Rab27a效应物JFC1和Munc13-4控制的新途径，这些途径调控脱颗粒、活性氧物种和中性粒细胞胞外陷阱的产生，以及内溶酶体信号转导。最后，我们讨论了了解这些分子机制的重要性，以便设计新的方法来有针对性地调节中性粒细胞介导的炎症过程。
Neutrophils constitute the first line of cellular defense against invading microorganisms and modulate the subsequent innate and adaptive immune responses. In order to execute a rapid and precise response to infections, neutrophils rely on preformed effector molecules stored in a variety of intracellular granules. Neutrophil granules contain microbicidal factors, the membrane-bound components of the respiratory burst oxidase, membrane-bound adhesion molecules, and receptors that facilitate the execution of all neutrophil functions including adhesion, transmigration, phagocytosis, degranulation, and neutrophil extracellular trap formation. The rapid mobilization of intracellular organelles is regulated by vesicular trafficking mechanisms controlled by effector molecules that include small GTPases and their interacting proteins. In this review, we focus on recent discoveries of mechanistic processes that are at center stage of the regulation of neutrophil function, highlighting the discrete and selective pathways controlled by trafficking modulators. In particular, we describe novel pathways controlled by the Rab27a effectors JFC1 and Munc13-4 in the regulation of degranulation, reactive oxygen species and neutrophil extracellular trap production, and endolysosomal signaling. Finally, we discuss the importance of understanding these molecular mechanisms in order to design novel approaches to modulate neutrophil-mediated inflammatory processes in a targeted fashion.
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