title: The origin of P-selectin as a circulating plasma protein.
abstract: P-selectin is a 140 kD protein found in the alpha-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 ED1-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 10(9)/l versus 241 x 10(9)/l 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.
authors.affiliation: Department of Hematology, University Hospital Utrecht, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Fijnheer
authors.forename: C J
authors.initials: CJ
authors.lastname: Frijns
authors.forename: J
authors.initials: J
authors.lastname: Korteweg
authors.forename: H
authors.initials: H
authors.lastname: Rommes
authors.forename: J H
authors.initials: JH
authors.lastname: Peters
authors.forename: J J
authors.initials: JJ
authors.lastname: Sixma
authors.forename: H K
authors.initials: HK
authors.lastname: Nieuwenhuis
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D015539:Platelet Activation; D011696:Purpura, Thrombocytopenic / Q000097:blood*; D013921:Thrombocytopenia / Q000097:blood*
chemical_list: D019007:P-Selectin