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

Nature volume 415, pages 175–179 (2002)Cite this article

Abstract

Activated platelets bind numerous adhesive and procoagulant proteins by receptor-mediated processes1. 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 α-granule factor V only on a subpopulation of cells2. Here we show that these cells, referred to as ‘COAT-platelets’, bind additional α-granule proteins, including fibrinogen, von Willebrand factor, thrombospondin, fibronectin and α2-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 (Mr) equal to CP15 plus 176. Serotonin, an abundant component of platelet-dense granules3, has an Mr 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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Figure 1: α-Granule proteins are concentrated on the surface of COAT-platelets.
Figure 2: Dansylcadaverine, acetyl-casein and anti-FXIII inhibit COAT-platelet production.
Figure 3: Serotonin conjugation to CP15 and fibrinogen.
Figure 4: Binding of biotin-BSA-(5-HT)6 to activated platelets.
Figure 5: COAT-platelets bind low levels of PAC-1.

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Acknowledgements

This work was supported in part by an NIH grant (G.L.D.), the W.K. Warren Medical Research Institute (G.L.D.), Novartis (L.A) and the Swiss National Science Foundation (K.J.C.).

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Authors and Affiliations

  1. W. K. Warren Medical Research Institute and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, Oklahoma, USA

    George L. Dale, Paul Friese, Peter Batar & Kenneth W. Jackson

  2. College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, Oklahoma, USA

    Stephen F. Hamilton

  3. Cardiovascular Biology Laboratory, Harvard School of Public Health, Boston, 02115, Massachusetts, USA

    Guy L. Reed

  4. Theodor Kocher Institute, University of Berne, Berne, CH-3012, Switzerland

    Kenneth J. Clemetson & Lorenzo Alberio

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Correspondence to George L. Dale.

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Dale, G., Friese, P., Batar, P. et al. Stimulated platelets use serotonin to enhance their retention of procoagulant proteins on the cell surface. Nature 415, 175–179 (2002). https://doi.org/10.1038/415175a

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