Department of Biological Sciences, University of Southern Mississippi, Hattiesburg, MS 39406, U.S.A.
Division of Fundamental Neurobiology, University Health Network, Toronto, Ontario, Canada M5T 2S8.
Biochem Soc Trans. 2018 Apr 17;46(2):235-247. doi: 10.1042/BST20170450. Epub 2018 Feb 22.
Mast cells play pivotal roles in innate and adaptive immunities but are also culprits in allergy, autoimmunity, and cardiovascular diseases. Mast cells respond to environmental changes by initiating regulated exocytosis/secretion of various biologically active compounds called mediators (e.g. proteases, amines, and cytokines). Many of these mediators are stored in granules/lysosomes and rely on intricate degranulation processes for release. Mast cell stabilizers (e.g. sodium cromoglicate), which prevent such degranulation processes, have therefore been clinically employed to treat asthma and allergic rhinitis. However, it has become increasingly clear that different mast cell diseases often involve multiple mediators that rely on overlapping but distinct mechanisms for release. This review illustrates existing evidence that highlights the diverse exocytic pathways in mast cells. We also discuss strategies to delineate these pathways so as to identify unique molecular components which could serve as new drug targets for more effective and specific treatments against mast cell-related diseases.
肥大细胞在先天和适应性免疫中发挥关键作用,但也是过敏、自身免疫和心血管疾病的罪魁祸首。肥大细胞通过启动各种生物活性化合物(称为介质)的调节性胞吐/分泌来响应环境变化(例如蛋白酶、胺类和细胞因子)。许多这些介质都储存在颗粒/溶酶体中,并且依赖于复杂的脱颗粒过程来释放。因此,肥大细胞稳定剂(例如色甘酸钠)已被临床用于治疗哮喘和过敏性鼻炎,因为这些稳定剂可以防止这种脱颗粒过程。然而,越来越明显的是,不同的肥大细胞疾病通常涉及多种介质,这些介质的释放依赖于重叠但不同的机制。这篇综述介绍了现有证据,强调了肥大细胞中存在多样化的胞吐途径。我们还讨论了划分这些途径的策略,以便确定可以作为新的药物靶点的独特分子成分,从而针对与肥大细胞相关的疾病进行更有效和更有针对性的治疗。