Leukocyte and endothelial adhesion molecule studies in knockout mice.

Ischemia and reperfusion of the myocardium initiate an inflammatory response directed against the myocardium, and many studies attribute a significant portion of this injury to leukocytes. Leukocyte and endothelial cell adhesion molecules are responsible for neutrophil-endothelial cell interactions in coronary vasculature following ischemia and reperfusion. Interactions between beta(2)-integrins and intercellular adhesion molecule-1 are responsible for firm adhesion of neutrophils to the coronary endothelium in acute cardiac inflammation. Leukocyte-expressed CD18 plays a crucial role, and genetic deficiency of CD18 significantly attenuates myocardial ischemia-reperfusion injury. Genetic deficiency of intercellular adhesion molecule-1 also minimizes myocardial necrosis following ischemia and reperfusion. The selectin family of adhesion glycoproteins also participates in various phases of leukocyte-endothelial interactions, and studies with P-selectin- and E-selectin-deficient mice have shown attenuation of both neutrophil accumulation and myocardial injury following myocardial ischemia and reperfusion.