BINDING AND METABOLISM OF HEPARIN BY ENDOTHELIAL CELLS

In this study we show that bovineadrenal capillary endothelial cells(BACE) contain heparin (HP); this HP has been found associated with the cell surface (i.e; trypsin-removable^and intracellularly. How-ever, experiments with [ sjsodium sulfate labelling, demonstrate that BACE cells donot synthesize HP de novo, but they uptake it from serum. We have studied binding, uptake, and metabolism odifferent molecular weight-HPs: 13 Kd-HP from bovine source, 14 Kd-HP from porcine source, 4.5 Kd, and 2.5-HP fragments. Comparison among different HPs, was carried out by calculating the IC from competition curves for [3HJ- HP. Binding of labelled-HP to BACE cells was specificand saturable. Dextran sulfate and glycosaminoglycans did not compete for binding; only heparan sulfate showed some competition. Binding of different HPs was strictly dependent on their molecular weight; 2.5 Kd- HP was unable to bind to cells, although sulfation degree of this fragment and of unfractionated HP was almost identical. Therefore, we assume that a specific oligosaccharide sequence could be responsible for HP binding to BACE cells; this hypothetical "binding sequence" could then be lost in very low molecular weight-HP fragments. BACE cells are also able to internalize HP, and they release its low molecular weight degradation products into culture medium. Thus we suggest that endothelial cells might represent a site for the metabolism of endogenous and exogenous HP in vivo.