Biological and binding studies of acidic fibroblast growth factor in the presence of substituted dextran

Author: Tardieu Michele   Slaoui Faouzi   Josefonvicz Jacqueline   Courty Jose   Gamby Chantal   Barritault Denis  

Publisher: Taylor & Francis Ltd

ISSN: 1568-5624

Source: Journal of Biomaterials Science, Polymer Edition, Vol.1, Iss.1, 1989-01, pp. : 63-70

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Abstract

—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 20μg of heparin or 400μg 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 0.2μg/ml. At 1μg/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 20μg/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. These receptors to heparin apparently do not have an affinity for DDE. Our data show that DDE can replace heparin in its interaction with aFGF and that it has the capacity to potentiate the biological activity of these growth factors. Furthermore, our binding studies suggest that this potentiation is not mediated through the cellular receptor of 125Ι-aFGF. The interaction of heparin with aFGF stabilizes and protects aFGF from chemical and proteolytic degradation. DDE may also be a useful aFGF stabilizer with much weaker hemostatic properties than heparin for in vivo application of FGF.