VASCULAR ENDOTHELIAL-CELL ACTIVATION AND PERMEABILITY RESPONSES TO THROMBIN

The serine protease, thrombin, evokes numerous endothelial cell respon ses which regulate hemostasis, thrombosis and vessel wall pathophysiol ogy. One such response, the development of intercellular gap formation and vascular permeability is relevant to each of these processes and is a cardinal features of inflammation. Regulation of endothelial cell gap formation and therefore permeability is a function of a dynamic b alance between competing adhesive, barrier-promoting tethering forces and contractile, tension-producing forces which result in barrier dysf unction. The key tethering events governing focal endothelial cell adh esion to the extracellular matrix and cell-cell interactions are poorl y understood In contrast, information is rapidly increasing regarding endothelial-specific contractile processes driven by the actomyosin mo lecular motor. The level of myosin light chain phosphorylation catalyz ed by a unique myosin light chain kinase promotes productive actin-myo sin interaction and governs the degree of centripetal tension produced . In this review the signal transducing and contractile mechanisms by which thrombin elicits endothelial cellular activation through its spe cific receptor are addressed. The pathways by which thrombin may alter the balance between contractile and tethering forces to promote endot helial cell gap formation are discussed.