Role of the cytoskeleton in neutrophil activation and inflammation

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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.