Mécanisme de recrutement des neutrophiles dans des conditions neuroinflammatoires
|Abstract:||The central nervous system (CNS) is constantly patrolled by leukocytes in order to protect tissue against pathogens and maintain homeostasic conditions. The main objective of this thesis was to characterize the biomolecular cascade responsible for leucocyte recruitment to the cerebral vasculature, during two neuroinflammatory conditions: pertussis toxin (PTX) exposure and experimental autoimmune encephalomyelitis (EAE). These leukocytes, presenting a particular "rod-shaped" morphology, have been first reported during examination of peripheric immune response in the central nervous system following induction of endotoxemia by lipopolysaccharide (LPS) administration. In the framework of this thesis, we first looked to characterize the identity of the rod-shaped leukocytes recruited to the brain vasculature during these neuroinflammatory conditions, which revealed to be mainly constitued of neutrophils. Starting with the hypothesis of a recruitment mechanism similar to the one induced by LPS, we uncovered the existence of an alternative mechanism of rod-shaped leukocytes recruitment that relies on interleukin 6 (IL-6), aM integrin, ICAM-1 adhesion molecule and CXCL1 chemokine during the two neuroinflammatory conditions. We sought to identify the molecular pathway responsible for cerebral endothelium activation that promote rod-shaped leukocytes to the CNS vasculature. These works allowed to confirm expression of IL-6Ra receptor on CNS vasculature but preliminary data regarding the involvement of classic IL-6 pathway in endothelium are inconclusives. This thesis contributes to identify a mechanism of neutrophil recruitment during neuroinflammatory contexts and suggests CXCL1 chemokine as a potential therapeutic target in the treatment of neuroinflammatory pathologies like multiple sclerosis.|
|Document Type:||Thèse de doctorat|
|Open Access Date:||24 April 2018|
|Collection:||Thèses et mémoires|
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