Endothelial adhesion molecules in health and disease.
One of the most important events in the reaction to all forms of injury is adhesion of leukocytes to endothelium, a prelude to their emigration into tissues. This process is central to inflammation, atherosclerosis, and immune reactions. Endothelial-leukocyte adhesion is governed largely by the interaction of complementary adhesion molecules on endothelia and leukocytes. The synthesis, surface expression, and avidity of these molecules, are regulated by chemical mediators, particularly chemokines. The most important adhesion molecule pairs are the selectins (E, L and P), the immunoglobulins ICAM-1 and VCAM-1, and the beta 2 and beta 1 integrins (e.g., LFA-1 and VLA-4). In vivo studies in experimental animals and humans have confirmed a role for these molecules in a number of pathological processes, including transplant rejection, septic shock, atherosclerosis, late phase hypersensitivity reactions, immunologically-mediated lung and kidney disease, and reperfusion injury. Besides their importance in understanding pathogenesis, work on adhesion molecules has direct clinical implications in diagnosis and therapy. Current studies suggest that the expression of these adhesion molecules may be a useful marker for active inflammation under certain conditions, and that abrogation of endothelial adhesion by interfering with such molecules may inhibit tissue injury. Mice genetically deficient in adhesion molecules (knock out) have been particularly useful in the study of the role of these molecules in vivo. This lecture will first summarize the state-of the-art on the structure, localization, and distribution of the major adhesion molecules, examine their roles in vivo, in humans and knock-out mice, and point to possible use of the information derived from these studies in diagnosis and therapy.
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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Cotran
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Mayadas-Norton
D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D007136:Immunoglobulins / Q000502:physiology; D016023:Integrins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009393:Nephritis / Q000503:physiopathology*; D012016:Reference Values; D019087:Selectins / Q000502:physiology
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; D019087:Selectins