Role of adhesion molecules in vascular regulation and damage.

Abstract

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 glycoproteins have been attributed to excessive production of cytokines and oxidants. The risk factors for cardiovascular disease, particularly diabetes mellitus and hypercholesterolemia, 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.