Ménasché Gaël, Longé Cyril, Bratti Manuela, Blank Ulrich
Laboratory of Molecular Basis of Altered Immune Homeostasis, Imagine Institute, INSERM UMR 1163, Université de Paris, Paris, France.
Centre de Recherche sur l'Inflammation, INSERM UMR 1149, CNRS ERL8252, Faculté de Médecine site Bichat, Université de Paris, Paris, France.
Front Cell Dev Biol. 2021 Mar 16;9:652077. doi: 10.3389/fcell.2021.652077. eCollection 2021.
Mast cells are well known for their role in allergies and many chronic inflammatory diseases. They release upon stimulation, e.g., via the IgE receptor, numerous bioactive compounds from cytoplasmic secretory granules. The regulation of granule secretion and its interaction with the cytoskeleton and transport mechanisms has only recently begun to be understood. These studies have provided new insight into the interaction between the secretory machinery and cytoskeletal elements in the regulation of the degranulation process. They suggest a tight coupling of these two systems, implying a series of specific signaling effectors and adaptor molecules. Here we review recent knowledge describing the signaling events regulating cytoskeletal reorganization and secretory granule transport machinery in conjunction with the membrane fusion machinery that occur during mast cell degranulation. The new insight into MC biology offers novel strategies to treat human allergic and inflammatory diseases targeting the late steps that affect harmful release from granular stores leaving regulatory cytokine secretion intact.
肥大细胞因其在过敏和许多慢性炎症性疾病中的作用而广为人知。例如，通过IgE受体刺激后，它们会从细胞质分泌颗粒中释放出多种生物活性化合物。颗粒分泌的调节及其与细胞骨架和运输机制的相互作用直到最近才开始被理解。这些研究为脱颗粒过程调节中分泌机制与细胞骨架成分之间的相互作用提供了新的见解。它们表明这两个系统紧密耦合，意味着存在一系列特定的信号效应器和衔接分子。在这里，我们回顾了最近的知识，这些知识描述了在肥大细胞脱颗粒过程中，与膜融合机制一起调节细胞骨架重组和分泌颗粒运输机制的信号事件。对肥大细胞生物学的新见解为治疗人类过敏性和炎症性疾病提供了新策略，这些策略针对影响颗粒储存中有害物质释放的后期步骤，同时保持调节性细胞因子分泌完整。
