Human β-thromboglobulin inhibits PGI₂ production and binds to a specific site in bovine aortic endothelial cells

Abstract

Blood platelets have a major role in haemostasis through their aggregation and adherence to the damaged vessel wall. During this process, platelet granular constituents are released. Although the functions of many of these release products are well known, biological functions of some well defined platelet specific proteins have not been determined. This category includes platelet factor 4 (PF4) and β-thromboglobulin (βTG), both small proteins of molecular weight 30,000–36,000 (refs 1, 2) which are stored in the α granule of the platelet and have not been detected in any other tissue. βTG is composed of four identical noncovalently bound subunits and its amino acid sequence is significantly homologous with that of PF4 (ref. 3). Although PF4 possesses a marked ability to neutralise heparin, no physiological or pathophysiological role has been attributed to either protein. The discovery of prostacyclin (PGI₂) has led to a reappraisal of the factors regulating haemostasis and especially of the role of the vascular endothelium in preventing platelet adherence and aggregation^4–6. The initial action of PGI₂ on the platelet is to stimulate adenylate cyclase^7–9, and it is the most potent inhibitor of platelet aggregation yet discovered. Also, cultures of arterial and venous endothelial cells have been found capable of producing PGI₂ (refs 10,11). We now report results indicating that βTG reduces the production of PGI₂-like activity in cultured bovine endothelial cells, which are shown to possess a specific receptor for βTG. The characteristics of this receptor suggest that βTG may act locally at high concentrations to favour platelet aggregation by diminishing PGI₂ production.