Figure 4. Infiltration of the infarcted myocardium with leukocytes is dependent on a sequence of adhesive interactions.
During the inflammatory phase of infarct healing, chemoattractants for neutrophils, monocytes and lymphocytes are upregulated in the injured myocardium. Local release of inflammatory mediators results in endothelial cell activation and surface expression of adhesion molecules. The selectin family of adhesion molecules mediates the initial capture of leukocytes from the rapidly flowing bloodstream to the blood vessel. Selectins promote leukocyte attachment and rolling (1) at shear stresses characteristic of post-capillary venules. Although rolling is a prerequisite for eventual firm adherence to blood vessels under conditions of flow, selectin-dependent adhesion of leukocytes does not lead to firm adhesion (2) and transmigration (3) unless another set of adhesion molecules, the integrins, is engaged. The mechanisms responsible for leukocyte transmigration into the tissues are poorly understood. In vitro studies have demonstrated that infiltrating neutrophils are capable of inducing cytotoxic injury to cardiomyocytes (4); this process is dependent on adhesive interactions between activated neutrophils and cytokine-stimulated cardiomyocytes. Whether neutrophil-mediated injury significantly contributes to cardiomyocyte death following infarction remains controversial (Symbols: Ly, lymphocyte; Mo, monocyte; Ma, macrophage; N, neutrophil; EC, endothelial cell; CM, cardiomyocyte).