BETA(3) INTEGRIN-MEDIATED FIBRIN CLOT RETRACTION BY NUCLEATED CELLS -DIFFERING BEHAVIOR OF ALPHA(IIB)BETA(3) AND ALPHA(V)BETA(3)

Fibrin clot retraction may be important in resolution of thrombi and, in platelets, is mediated by integrin alpha(IIb)beta(3) (GPIIb-IIIa). Nucleated cells that lack alpha(IIb)beta(3) can retract fibrin clots, and we now report that integrin alpha(v) beta(3) can support this proc ess. In addition, we compared the capacities of recombinant beta(3) in tegrins to mediate clot retraction in Chinese hamster ovary and M21 me lanoma cells. We found that alpha alpha(v) beta(3), but not alpha(IIb) beta(3) could spontaneously support retraction. Transferring the cytop lasmic domain of alpha(v) to alpha(IIb) enabled the resulting chimeric alpha(IIb)beta(3) to support clot retraction. The capacity of the alp ha(v) cytoplasmic domain to support clot retraction was not caused by activation of the ligand binding function of alpha(IIb)beta(3) or by e nhancement of alpha(IIb)beta(3)'s capacity to stimulate the formation of focal adhesions or the tyrosine phosphorylation of pp125(FAK). Thes e experiments define requirements for alpha(IIb)beta(3)-mediating clot retraction, establish the capacity of alpha(v) beta(3) to mediate thi s process, and suggest differing functional roles of the alpha(v) and alpha(IIb) cytoplasmic domains. (C) 1995 by The American Society of He matology.