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.
Grotendorst
G R
GR
Department of Ophthalmology, College of Medicine, University of South Florida, Tampa 33612.
Igarashi
A
A
Larson
R
R
Soma
Y
Y
Charette
M
M
D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
D010716:Phosphatidylinositols; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor