Neutralizing antibodies inhibit the binding of basic fibroblast growth factor to its receptor but not to heparin.
Polyclonal antibodies were prepared against recombinant basic fibroblast growth factor (bFGF) that reacted only with bFGF but not acidic FGF. These antibodies were able to inhibit various biological activities of bFGF such as the ability of bFGF to stimulate DNA synthesis in 3T3 cells, proliferation and migration of bovine capillary endothelial cells (BCEC), and neurite extension in pheochromocytoma (PC12) cells. The anti-bFGF antibodies also inhibited the mitogenic activity of subendothelial cell extracellular matrix for BCEC, demonstrating that the growth factor component in extracellular matrix required for supporting BCEC proliferation was bFGF. Anti-bFGF antibodies inhibited the cross-linking of bFGF to its high affinity receptor on BCEC cells. However, these antibodies did not inhibit the binding of bFGF to heparin-Sepharose or to the low affinity receptors of BCEC which have been demonstrated to be heparin-like molecules. These results suggest that bFGF has distinct domains for binding to high affinity cellular receptors and for binding to heparin.
Kurokawa
M
M
Department of Surgery, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Doctrow
S R
SR
Klagsbrun
M
M
D000818:Animals; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001665:Binding Sites; D002417:Cattle; D002455:Cell Division; D002633:Chemotaxis; D004730:Endothelium, Vascular / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000276:immunology* / Q000378:metabolism; D006493:Heparin / Q000378:metabolism*; D066298:In Vitro Techniques; D009500:Neutralization Tests; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017468:Receptors, Fibroblast Growth Factor
D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D006493:Heparin