Adhésion leucocytes-endothélium et interaction des voies de mécano-transduction chez la cellule endothéliale

Abstract : Many biochemical and mechanical factors are involved in cardio-vascular diseases, such atherosc lerosis, thrombosis and inflammation. Chemotactic substances secreted by damaged tissues induce bi-directional activation of both leukocytes and endothe lial cells (EC) to generate leukocyte/endothelium adhesion whereas local hemodynamic changes induce morphological and functional modifications on EC through a mechanotransduction process. The aim of this study was to investigate adhesion forces of leukocytes on 3 biological substrates (fibrinogen, EC and activated EC) with flow chamber system and mechanotransductor interactions during early and late response of EC. First adhesion force of leukocytes on the substrate depends of their activation state, of adhesion molecules localization and expression on cell surface whereas detachment process depends of the substrate. Second, we completed the mechano-transduction model. Flow stimulation of EC acts through the liaison site of integrins to induce the formation of [alpha]v[beta]3 integrin-Shc complexes which are partly dependent of intracellular calcium concentration and Gi-prote in activity. This carly response of EC is necessary to flow-dependent JNK late response by the liaison site of integrins and whieh depends of intracellular calcium concentration and Gi-protein activity. Ali of these results suggest that biochemical and hemodynamic modifications of local environment modulate cell functions during atherogenesis, thrombosis and inflammation.
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Marie-Vénus Labrador. Adhésion leucocytes-endothélium et interaction des voies de mécano-transduction chez la cellule endothéliale. Autre. Université Henri Poincaré - Nancy 1, 2001. Français. ⟨NNT : 2001NAN11320⟩. ⟨tel-01746418⟩

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