Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface

被引:256
作者
Dale, GL [1 ]
Friese, P
Batar, P
Hamilton, SF
Reed, GL
Jackson, KW
Clemetson, KJ
Alberio, L
机构
[1] Univ Oklahoma, Hlth Sci Ctr, WK Warren Med Res Inst, Oklahoma City, OK 73104 USA
[2] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK 73104 USA
[3] Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Oklahoma City, OK 73104 USA
[4] Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA
[5] Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland
关键词
D O I
10.1038/415175a
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Activated platelets bind numerous adhesive and procoagulant proteins by receptor-mediated processes(1). Although there is little evidence to suggest that these processes are heterogeneous in platelets, we previously found that platelets co-stimulated with collagen and thrombin express functional alpha -granule factor V only on a subpopulation of cells(2). Here we show that these cells, referred to as 'COAT-platelets', bind additional alpha -granule proteins, including fibrinogen, von Willebrand factor, thrombospondin, fibronectin and alpha (2)-antiplasmin. These proteins are all transglutaminase substrates, and inhibitors of transglutaminase prevent the production of COAT-platelets. A synthetic transglutaminase substrate (CP15) also binds to COAT-platelets, and analysis by high performance liquid chromatography/mass spectrometry shows that a product is formed with a relative molecular mass (M-r) equal to CP15 plus 176. Serotonin, an abundant component of platelet-dense granules(3), has an M-r of 176, and fibrinogen isolated from COAT-platelets contains covalently linked serotonin. Synthetic bovine serum albumin-(serotonin)(6) binds selectively to COAT-platelets and also inhibits the retention of procoagulant proteins on COAT-platelets. These data indicate that COAT-platelets use serotonin conjugation to augment the retention of procoagulant proteins on their cell surface through an as yet unidentified serotonin receptor.
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页码:175 / 179
页数:5
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