The origin of P-selectin as a circulating plasma protein

R. Fijnheer, C. J M Frijns, J. Korteweg, H. Rommes, J. H. Peters, J. J. Sixma, H. K. Nieuwenhuis

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

P-selectin is a 140 kD protein found in the α-granules of platelets and the Weibel-Palade bodies of endothelial cells. On cell activation it is expressed on the cell surface and also secreted into plasma. Whether the circulating soluble P-selectin (sP-selectin) originates from platelets, endothelial cells, or both, is not known. We studied the level of sP-selectin in diseases with different platelet counts, with or without evidence of endothelial cell activation. Endothelial cell activation was confirmed by the detection of sE-selectin and ED l-fibronectin. A significant positive correlation between platelet count and sP-selectin concentration was observed in healthy controls, and in patients with thrombocytopenia due to bone marrow aplasia, or with thrombocytosis (r = 0.85; n = 47; p < 0.001). In patients with idiopathic thrombocytopenic purpura (ITP) the sP-selectin concentration was 110 ± 39 ng/ml (n = 10), compared to 122 ± 38 ng/ml in healthy controls (n = 26). However, their mean platelet count was lower (58 X 109/1 versus 241 X 109/1 in the control group). Accordingly, the levels of sP-selectin expressed per platelet increased to significantly higher levels (2.0 ± 1.2 versus 0.6 ± 0.2 fg/platelet in the control group; p < 0.0001). This suggests increased platelet turnover in patients with ITP. High levels of sP-selectin were found in patients with sepsis (398 ± 203 ng/ml; n = 15) and with thrombotic thrombocytopenic purpura (TTP; 436 ± 162 ng/ml; n = 12). Compared with patients with ITP, the concentration of sP-selectin per platelet was higher in patients with sepsis (4.8 ± 4.3 fg/platelet; p < 0.005) or TTP (17.1 ± 9.5 fg/platelet; p < 0.001). Endothelial cells are very likely to be the source in these patients and the presence of endothelial cell activation was confirmed by increased levels of circulating E-selectin and ED1-fibronectin. This study suggests that platelets are the major source of circulating sP-selectin in healthy individuals. Endothelial cell activation is associated with an increased sP-selectin concentration per platelet.

Original languageEnglish (US)
Pages (from-to)1081-1085
Number of pages5
JournalThrombosis and Haemostasis
Volume77
Issue number6
StatePublished - Jun 1997
Externally publishedYes

ASJC Scopus subject areas

  • Hematology

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