Role of the cytoskeleton in neutrophil activation and inflammation

细胞骨架在中性粒细胞活化和炎症中的作用

• 批准号: 203418-2009
• 负责人: Girard, Denis
• 金额: $ 4.08万
• 依托单位: Institut national de la recherche scientifique
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2010
• 资助国家: 加拿大
• 起止时间: 2010-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=453312
• 关键词: Role; cytoskeleton; neutrophil; activation; inflammation

The cell cytoskeleton is a dynamic structure that is targeted by several anti-cancer drugs to arrest cell proliferation. Upon stimulation, a significant re-organization of the cytoskeleton occurs in a variety of cells. The present research program focuses on one cell type of the immune system, the mature non-dividing neutrophil that is a key player in inflammation. Especially, re-organization of the cytoskeleton occurs in activated neutrophils during different cell functions, including adhesion, locomotion, respiratory burst, degranulation, phagocytosis and apoptosis. As we have recently documented in these cells, several, but not all, cytoskeletal proteins are cleaved by caspases in spontaneous or agent-induced neutrophil cell apoptosis. This suggests the existence of a regulated control mechanism. The main objective of the proposed research program is to elucidate the role of the different cytoskeletal structures (microfilaments, intermediate filaments, and microtubules) in the general cell biology and physiology of the neutrophil. Our research interests focus on the inflammatory response by studying the neutrophil cell physiology in response to a variety of molecules such as drugs, cytokines, plant lectins and even environmental contaminants during inflammation in vivo as well as during ex vivo and in vitro activation.

细胞骨架是一种动态结构，被几种抗癌药物靶向以阻止细胞增殖。在刺激时，在各种细胞中发生细胞骨架的显著重组。目前的研究计划集中在免疫系统的一种细胞类型，成熟的非分裂中性粒细胞，这是炎症的关键球员。尤其是活化的中性粒细胞在不同的细胞功能中，包括粘附、运动、呼吸爆发、脱粒、吞噬和凋亡，都发生细胞骨架的重组。正如我们最近在这些细胞中所记录的，在自发或药物诱导的中性粒细胞凋亡中，有几种但不是全部的细胞骨架蛋白被半胱天冬酶切割。这表明存在一个规范的控制机制。拟议的研究计划的主要目标是阐明不同的细胞骨架结构（微丝，中间丝和微管）在中性粒细胞的一般细胞生物学和生理学中的作用。我们的研究兴趣集中在炎症反应，通过研究中性粒细胞生理学响应于各种分子，如药物，细胞因子，植物凝集素，甚至环境污染物在体内炎症以及在离体和体外激活。