Role of adhesion molecules in vascular regulation and damage

The trafficking of leukocytes within the microcirculation is critical for normal immune surveillance of tissues. The process of leukocyte recruitment is tightly regulated by the sequential expression and activation of specific adhesion molecules on the surface of leukocytes and endothelial cells. These adhesion molecules mediate distinct steps in the recruitment of leukocytes in the microcirculation. The selectins mediate leukocyte rolling, whereas glycoproteins belonging to the integrin and immunoglobulin supergene families enable leukocytes to firmly adhere and emigrate in venules. The leukocyte-endothelial cell adhesion that is mediated by these adhesion molecules has been shown to alter the function of endothelial cells in all segments of the vasculature (ie, in arterioles, capillaries, and venules). Diseases such as ischemia-reperfusion, hypertension, and atherosclerosis exhibit vascular changes that are characteristic of acute or chronic inflammatory responses. These vascular alterations are associated with, and influenced by, changes in the avidity and density of adhesion molecules on the surface of either endothelial cells, leukocytes, or both. The activation and increased expression of these adhesion glyco-proteins have been attributed to excessive production of cytokines and oxidants. The risk factors for cardiovascular disease, particularly diabetes mellitus and hypercholester-olemia, appear to sensitize the microvasculature to these inflammatory stimuli, thereby rendering tissues more vulnerable to the deleterious effects of ischemia and reperfusion. These findings raise the possibility of applying therapeutic strategies that are directed against adhesion molecules for the management of some cardiovascular diseases tion, and stroke [1,2,3]. The cell-cell interactions that are mediated by these adhesion glycoproteins are expressed on the surface of activated leukocytes and endothelial cells. Whereas endothelial cells in all vascular segments (arteries, capillaries, and veins) can express adhesion molecules that interact with specific ligands on leukocytes, postcapillary venules usually represent the primary locus of the inflammatory response because the density of endothelial adhesion molecules is greatest in this vascular segment. The leukocyte-endothelial cell interactions typically observed in inflamed venules occur in a sequential, coordinated manner that involves three distinct steps-rolling, firm adhesion (adherence), and emigration (Fig. 1). Each step is tightly regulated by the sequential activation and expression of different families of adhesion molecules, either on the circulating leukocyte or vascular endothelium, namely selectins, β2-integrins, and supergene immunoglobulins (Table 1) [4]. These families of adhesion molecules are described here and followed by a discussion of the pathophysiologic significance of adhesion molecules in different animal models of cardiovascular disease. Copyright © 2000 by Current Science Inc.