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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3578-3587.)
© 1997 American Heart Association, Inc.

Articles

Native Macromolecular Heparin Proteoglycans Exocytosed From Stimulated Rat Serosal Mast Cells Strongly Inhibit Platelet-Collagen Interactions

Riitta Lassila; Ken Lindstedt; ; Petri T. Kovanen

From the Wihuri Research Institute, Helsinki, Finland.

Correspondence to Riitta Lassila, Wihuri Research Institute, Kalliolinnantie 4, SF-00140 Helsinki, Finland. E-mail riitta.lassila{at}wri.fimnet.fi.

Abstract Mast cells, the major source of tissue heparin, line the vascular system. On stimulation, rat serosal mast cells release soluble heparin proteoglycans (HEP-PGs) of very high molecular weight (750 000). We compared the effects of HEP-PGs and standard heparins (average molecular weights, 15 000 and 5 000) on platelet-collagen interactions in vitro. In contrast with the standard heparins, HEP-PGs completely inhibited collagen-induced platelet aggregation and serotonin release in platelet-rich plasma. The inhibition caused by HEP-PGs depended on its macromolecular structure. In flowing blood, HEP-PGs also inhibited platelet deposition on a collagen-coated surface both at low and high shear rates. Although HEP-PGs did not block glycoprotein (GP) Ia/IIa-mediated platelet adhesion, they attenuated subsequent platelet activation and aggregation, as well as fibrinogen binding to platelets after collagen stimulation. HEP-PGs did not bind to platelets but bound tightly to von Willebrand factor (vWf) and enhanced its binding to collagen. Although platelet adhesion at high shear rate and vWf binding to GP Ib after ristocetin stimulation were not markedly affected, HEP-PGs reduced thrombin-induced aggregation and vWf binding to GP IIb/IIIa. These findings imply that activation of vascular mast cells with ensuing secretion of HEP-PGs may locally attenuate the thrombogenicity of matrix collagen by inhibiting its platelet-activating capacity.

Key Words: collagen • heparin • mast cells • platelet • thrombosis

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