Macrophage recognition of ICAM-3 on apoptotic leukocytes

Cells undergoing apoptosis are cleared rapidly by phagocytes, thus preventi ng tissue damage caused by loss of plasma membrane integrity. In this study , we show that the surface of leukocytes is altered during apoptosis such t hat the first Ig-like domain of ICAM-3 (CD50) can participate in the recogn ition and phagocytosis of the apoptotic cells by macrophages, Macrophage re cognition of apoptotic cell-associated ICAM-3 was demonstrated both on leuk ocytes and, following transfection of exogenous ICAM-3, on nonleukocytes, T he change in ICAM-3 was a consistent consequence of apoptosis triggered by various stimuli, suggesting, that it occurs as part of a final common pathw ay of apoptosis, Alteration of ICAM-3 on apoptotic cells permitting recogni tion by macrophages resulted in a switch in ICAM-3-binding preference from the prototypic ICAM-3 counterreceptor, LFA-1, to an alternative macrophage receptor, Using mAbs to block macrophage/apoptotic cell interactions, we we re unable to obtain evidence that either the, alternative ICAM-3 counterrec eptor alpha(d)beta(2) or the apoptotic cell receptor alpha(v)beta(3), was i nvolved in the recognition of ICAM-3. By contrast, mAb blockade of macropha ge CD14 inhibited ICAM-3-dependent recognition of apoptotic cells. These re sults show that ICAM-3 can function as a phagocytic marker of apoptotic leu kocytes on which it acquires altered macrophage receptor-binding activity.