Expression and Function of the Leukocyte Integrins in Medicine

The leukocyte integrins are essential membrane receptors that mediate leukocyte adhesion to various cells during immune and inflammatory responses including tumor cell killing, leukocyte migration from the bloodstream into inflamed tissues, and phagocytosis of bacteria. The importance of these receptors is underscored in humans with leukocyte adhesion deficiency (LAD), that is caused by the absence or greatly reduced expression of the leukocyte integrins on leukocytes, and which leads to recurrent life-threatening infections and impaired wound healing. These receptors can also exacerbate the diseased state when excessive accumulation of leukocytes occurs at the site of inflammation because of overexpression or increased activation of the leukocyte integrins on these cells. These receptors are involved in a variety of pathological conditions in the vascular system including ischemic reperfusion injury, stroke, and atherosclerosis. The leukocyte integrins augment tissue damage that occurs in autoimmune diseases including rheumatoid arthritis, multiple sclerosis, Crohn's disease, and ulcerative colitis. This review will focus on the molecular mechanisms that regulate activation of the leukocyte integrins including transcriptional control of leukocyte gene expression and the role these receptors play in normal and pathological inflammatory processes. Their potential use as markers for disease diagnosis and the prospects for anti-adhesion therapy to ameliorate disease as indicted in a number of animal models will be discussed.