The relevance of blood cell-vessel wall adhesive interactions for vascular thrombotic disease

Abstract

Activation and signaling of circulating blood and vessel wall cells, as well as their direct adhesive interactions, are critical for the regulation of vascular homeostasis related to vasomotor responses, inflammation, hemostasis, and wound repair. Under conditions of stress, inflammation, or infection the targeting and anchoring of leukocytic cells to the vascular endothelium is mediated by specific pairs of adhesion receptors and their counter-ligands that may induce juxtacrine signaling resulting in the expression of prothrombotic agonists such as tissue factor. Concomitant action of inflammatory cytokines may down-regulate thromboprotective mechanisms of the endothelium. Through similar intercellular interactions, the platelets recruited to these inflamed sites may aggregate and modulate leukocyte function. In addition, leukocytes can influence coagulation by their ability to produce pro- and anticoagulant factors as well as by providing specific receptors (such as Mac-1 or EPR-1) that serve as direct molecular links between inflammation and hemostasis. The initiation and amplification of blood clotting reactions on the leukocyte surface has consequences on other vascular cell functions and involves (cytokine) activation and signaling pathways that contribute to pathophysiological aspects of inflammatory responses. As a consequence, the diverse cell-to-cell interactions, as well as different inflammatory mediators or bidirectional signaling pathways, appear to be promising targets for the treatment of thrombotic complications in the context of inflammation-dependent vascular diseases.