Elastase-mediated release of heparan sulfate proteoglycans from pulmonary fibroblast cultures - A mechanism for basic fibroblast growth factor (bFGF)release and attenuation of bFGF binding following elastase-induced injury

We have investigated elastase-mediated alterations in the expression of bas ic fibroblast growth factor (bFGF) receptors and proteoglycan co-receptors and characterized the subsequent effects on bFGF receptor binding profiles. For these studies, pulmonary fibroblast cultures were treated with porcine pancreatic elastase, and elastase-mediated changes in bFGF receptor expres sion and binding profiles were assessed. Quantitation of [S-35]sulfate-labe led proteoglycan and total glycosaminoglycan release from fibroblast matric es indicated that elastase treatment released sulfated proteoglycan from th e cell surface in a time- and dose-dependent fashion that correlated strong ly with elastase-mediated bFGF release. Ligand binding studies indicated th at elastase treatment decreased total binding of I-125-bFGF to the cell sur face and affected both fibroblast growth factor receptor and heparan sulfat e proteoglycan (HSPG) binding sites. Western blot analyses indicated that e lastase treatment did not release significant amounts of fibroblast growth factor receptor protein. These findings indicate that elastase-mediated HSP G release from fibroblast matrices reduces the effective affinity of bFGF f or its receptor. Collectively, these studies suggest that HSPG co-receptors are important mediators of the pulmonary fibroblast response to elastase t reatment and that bFGF, HSPG, and other elastase-released entities play an important role in the response of the lung to chronic injury.