DIFFERENTIAL BINDING, BIOLOGICAL AND BIOCHEMICAL ACTIONS OF RECOMBINANT PDGF AA, AB, AND BB MOLECULES ON CONNECTIVE-TISSUE CELLS

We have compared the biological and biochemical properties of recombinant PDGF AA, AB, and BB using three types of fibroblastic cells: NIH/3T3, human skin fibroblast, and fetal bovine aortic smooth muscle. PDGF binding, receptor autophosphorylation, phosphatidyl inositol hydrolysis, as well as chemotactic and mitogenic responses of the cells were analyzed. PDGF-AB and PDGF-BB showed similar receptor binding, receptor autophosphorylation, and potent biological activity for all three of the cell types tested. In contrast, PDGF-AA was biologically active only for the NIH/3T3 cells in which binding sites for PDGF-AA were abundant, but was inactive for bovine aortic smooth muscle cells and human skin fibroblasts in which binding sites for PDGF-AA were absent. PDGF-AA could not induce any biochemical changes in the human skin fibroblasts or smooth muscle cells. Western blot studies with anti-Type alpha and beta-PDGF receptor antibodies indicate that the NIH/3T3 cells contained both PDGF alpha and beta-receptors, whereas the human skin fibroblasts and bovine smooth muscle cells contained only detectable levels of beta-receptors. These results indicate that cells possessing high levels of PDGF beta-receptors only are capable of responding equally well to either PDGF AB or BB.