Protective Effects of Monoclonal Antibodies to Cell Adhesion Glycoproteins in Models of Cardiac Reperfusion Injury and Leukocyte/Vascular Responses

Abstract

Prompt reperfusion of an ischemic tissue is necessary for restoration of function but can be associated, paradoxically, with the progressive deterioration of reversibly damaged cells resulting in dysfunction and necrosis (Braunwald 1985; Heras et al. 1988). This reperfusion injury has been studied extensively in models of myocardial ischemia (Lehr et al. 1993; Lefer et al. 1994) but has also been implicated in delayed graft function and rejection following cardiac allograft transplantation (Land 1994). The cause of reperfusion injury is no doubt multifactorial and is believed to involve an inappropriate infiltration of leukocytes and the subsequent release of their cytotoxic mediators into the previously ischemic tissue (Pinckard et al. 1983; Mullane et al. 1984). The leukocytic infiltrate has been implicated in the alteration of tissue function which can lead to cell death and organ failure. Leukocyte adhesion to the vascular endothelium, and subsequent migration into the ischemic myocardium or into a transplanted heart is orchestrated by a series of ligand-receptor events between leukocyte and endothelial cell surface glycoproteins (Lipsky et al. 1993). The importance of the various cell adhesion glycoproteins in mediating tissue damage in preclinical models of these disease states has been addressed with the administration of monoclonal antibodies (MAbs) which recognize and neutralize the function of the particular glycoproteins.