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

Riitta Lassila, Ken Lindstedt, Petri T. Kovanen
1997 Arteriosclerosis, Thrombosis and Vascular Biology  
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
more » ... a. The inhibition caused by HEP-PGs depended on its macromolecular structure. In flowing blood, HEP-PGs also inhibited platelet deposition on a collagencoated 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 activa-M ast cells are prevalent in the adventitial layer of vessel walls and in the perivascular areas of venules. 1, 2 They are also present in the arterial intima, the site of atherogenesis, 3 and activated mast cells have been found to infiltrate into the inflammatory shoulder regions of coronary atheromas, the most common site of rupture. 4, 5 On activation, such as that occurring during inflammation, mast cells degranulate and exocytose an array of potent vasoactive mediators, of which the short-lived leukotrienes and prostaglandins, platelet-activating factor, and histamine are known to stimulate platelets. Histamine releases endothelial vWf and P-selectin, two factors that are important adhesive signals to platelets and leukocytes. 6, 7 Furthermore, mast cells secrete glycosaminoglycans from which the clinically used heparins are derived, 8 whereas activated platelets secrete platelet factor 4, a heparinneutralizing factor, and heparitinase, a heparin-cleaving endoglycosidase. 9,10 Thus, there appears to be an interplay between these two cell types after their activation, which has been, however, poorly characterized at present. Whether mast cell activation is involved in hemostasis can be evaluated during anaphylaxis and in mastocytosis, two clinical conditions in which mast cells become excessively activated." Yet in these conditions, throm-
doi:10.1161/01.atv.17.12.3578 pmid:9437208 fatcat:egcnxfozybcvxcky4ny3sa2tgi