Role of the cytoskeleton in neutrophil activation and inflammation

细胞骨架是一种动态结构，是几种抗癌药物阻止细胞增殖的靶点。在刺激下，细胞骨架在各种细胞中发生显著的重组。目前的研究计划集中在免疫系统的一种细胞类型上，即成熟的不分裂的中性粒细胞，它是炎症的关键参与者。尤其是在不同的细胞功能过程中，包括黏附、运动、呼吸爆发、脱颗粒、吞噬和细胞凋亡，激活的中性粒细胞都会发生细胞骨架的重新组织。正如我们最近在这些细胞中所记录的那样，在自发或药物诱导的中性粒细胞凋亡中，有几个但不是全部的细胞骨架蛋白被caspase切割。这表明存在一种受监管的控制机制。该研究计划的主要目的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。我们的研究重点是通过研究中性粒细胞对多种分子如药物、细胞因子、植物凝集素甚至环境污染物在体内炎症过程中以及在体外和体外激活过程中的反应而产生的炎症反应。

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.