The Origin of P-selectin as a Circulating Plasma Protein

Abstract

SummaryP-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 EDl-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 ED 1 -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.

Soluble P-selectin levels during normal pregnancy: a longitudinal study

“…This higher concentration of sP-selectin observed in normal pregnancy is suggestive of increased platelet activation. Although both endothelial cells and platelets express P-selectin, previous studies have reported that sP-selectin is not primarily a product of the endothelium, but rather, that platelets are the major source of sP-selectin in normal controls 13,14 and in thrombotic and prethrombotic conditions 15 . Fijnheer et al 14 previously reported sP-selectin concentration per platelet to be a measure of endothelial cell activation.…”

“…Platelet mass was calculated by multiplying platelet count (Â10 9 /L) by mean platelet volume (fL). Concentration of sP-selectin per platelet was calculated by dividing the sP-selectin concentration (ng/mL) by the individual platelet count (Â10 9 /L), as described by Fijnheer et al 14 .…”

Atrial fibrillation and platelet reactivity

“…Even if P-selectin has been recognized in endothelial cells it is apparent that the greater quantity if not all soluble P-selectin evolves from platelets [6]. It has been suggested that soluble P-selectin reflects platelet activity over a long period of time.…”

In Search for Novel Biomarkers of Acute Coronary Syndrome

“…Thus, P-selectin is a marker of platelet activation which in turn is prerequisite for thrombosis (Serebruany et al, 1999a). Fijnheer et al (1997) have concluded that endothelial cell activation is associated with an increased P-selectin concentration per platelet. Elevated levels have been reported not only in AMI and unstable angina but also in stable angina.…”