Biological and binding studies of acidic fibroblast growth factor in the presence of substituted dextran.
Heparin has been shown to interact with acidic fibroblast growth factor (aFGF) and to potentiate the biological activity of aFGF on fibroblastic cells. Water-soluble dextran substituted with methyl carboxylic benzylamine and sulfonate groups has been shown to mimic the effect of heparin in its anticoagulant and anticomplement activity. We have studied the effect of a dextran derivative named E (DDE), which had an anticoagulant activity equivalent to 0.5 IU heparin/mg, on the mitogenic activity of aFGF on Chinese hamster fibroblasts (CCL39). DDE interacts with aFGF in a comparable manner to heparin. We have shown that 20 micrograms of heparin or 400 micrograms of DDE added to 1 ml of culture medium has no effect on cell proliferation alone but potentiates the mitogenic activity of aFGF ten fold if aFGF is added at doses corresponding to half maximum stimulation (ED50). We have also studied the effect of various concentrations of heparin and DDE on the binding of 125I-aFGF on bovine brain membranes. Interestingly, the binding of 125I-aFGF increased three-fold as the concentration of heparin was increased up to 0.2 microgram/ml. At 1 microgram/ml of heparin, the amount of bound 125I-aFGF is comparable to that obtained in the absence of heparin. At higher concentrations, heparin displaces bound 125I-aFGF, and a 50% displacement is seen with 20 micrograms/ml of heparin. In the presence of DDE, no increase in 125I-aFGF binding is seen and a displacement is obtained with increasing doses. A possible explanation of these results may be the existence of specific receptors to heparin on the cellular membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Tardieu
M
M
Laboratoire des cellules eucaryotes, Université Paris XII, Creteil, France.
Slaoui
F
F
Josefonvicz
J
J
Courty
J
J
Gamby
C
C
Barritault
D
D
D000818:Animals; D000925:Anticoagulants; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003911:Dextrans / Q000494:pharmacology*; D016220:Fibroblast Growth Factor 1 / Q000187:drug effects* / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor
D000925:Anticoagulants; D003911:Dextrans; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D016220:Fibroblast Growth Factor 1; D006493:Heparin