INTEGRIN ALPHA(V)BETA(3) DIFFERENTIALLY REGULATES ADHESIVE AND PHAGOCYTIC FUNCTIONS OF THE FIBRONECTIN RECEPTOR ALPHA(5)BETA(1)

The plasma protein fibronectin is an important opsonin in wound repair and host defense. To better understand the process of fibronectin-mediated phagocytosis, we have transfected K562 cells, which endogenously express alpha(5) beta(1), with alpha(v) beta(3). In these transfectants, antibodies to alpha(v) beta(3) block phagocytosis of fibronectin-opsonized beads completely, even though half the ingestion occurs through endogenous alpha(5) beta(1) receptors. alpha(5) beta(1)-mediated adhesion to fibronectin-coated surfaces is unaffected by alpha(v) beta(5) ligation. Neither alpha(v) beta(5) nor alpha(M) beta(2) ligation affects alpha(5) beta(1)-phagocytic function in transfectants expressing these receptors. Pharmacologic data suggest that alpha(v) beta(5) ligation suppresses the phagocytic competence of high affinity alpha(5) beta(1)-receptors through a signal transduction pathway, perhaps involving protein kinase C. In addition to its significance for phagocytosis, alpha(v) beta(3) regulation of alpha(s) beta(1) function may be significant for its roles in cell migration, metastasis, and angiogenesis.