NATIVE MACROMOLECULAR HEPARIN PROTEOGLYCANS EXOCYTOSED FROM STIMULATED RAT SEROSAL MAST-CELLS STRONGLY INHIBIT PLATELET-COLLAGEN INTERACTIONS

Mast cells, the major source of tissue heparin, line the vascular syst em. On stimulation, rat serosal mast cells release soluble heparin pro teoglycans (HEP-PGs) of very high molecular weight (750 000). We compa red the effects of HEP-PGs and standard heparins (average molecular we ights, 15 000 and 5 000) on platelet-collagen interactions in vitro. I n contrast with the standard heparins, HEP-PGs completely inhibited co llagen-induced platelet aggregation and serotonin release in platelet- rich plasma. The inhibition caused by HEP-PGs depended on its macromol ecular structure. In flowing blood, HEP-PGs also inhibited platelet de position on a collagen-coated surface both at low and high shear rates . Although HEP-PGs did not block glycoprotein (GP) Ia/IIa-mediated pla telet adhesion, they attenuated subsequent platelet activation and agg regation, as well as fibrinogen binding to platelets after collagen st imulation. HEP-PGs did not bind to platelets bur bound tightly to von Willebrand factor (vWf) and enhanced its binding to collagen. Although platelet adhesion at high shear rare and vWf binding to GP Ib after r istocetin stimulation were not markedly affected, HEP-PGs reduced thro mbin-induced aggregation and vWf binding to GP IIb/IIIa. These finding s imply that activation of vascular mast cells with ensuing secretion of HEP-PGs may locally attenuate the thrombogenicity of matrix collage n by inhibiting its platelet-activating capacity.