Platelet integrin (GPIIb-IIIa) plays important roles in platelet-mediated clot retraction. However, little is known about the mechanisms of clot retraction mediated by nucleated cells. In this report, we demonstrate that another member of the integrin family, , is involved in clot retraction mediated by nucleated cells. Retraction of fibrin clots was observed using a human melanoma cell line, C32TG, which contains no complex. This retraction was inhibited by RGD-containing peptide, monoclonal anti-, and anti- antibodies. Immunoelectron microscopic studies revealed a direct interaction between integrin and fibrin fibers at an early stage of clot retraction. We found that another human embryonal cell line, 293, which is known to express , but no , lacks fibrin gel retractile activity. Upon transfection of DNA into 293 cells, the subunit formed a complex with an endogenous subunit. The -bearing transfectants were found to retract fibrin gels, which was specifically inhibited by anti- antibody. In addition, a point mutation at Asp in the ligand binding domain abolished the clot retractile activity of 293 transfectants, indicating the requirement of ligand-binding activity. Our findings suggest that is involved in mediating the interaction between the three-dimensional fibrin network and nucleated cells and in promoting ``post-receptor occupancy'' events.

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