Expression of platelet P-selectin and detection of soluble P-selectin, NPYand RANTES in patients with inflammatory bowel disease

Objective and Design: P-selectin, a membrane glycoprotein which is expresse d on activated platelets and endothelial cells, plays a crucial role in the inflammatory response. The main action is adhesion of leukocytes, facilita tion of diapedesis and induction of cytokine production from monocytes (MCP -1 and IL-8), mediated via RANTES released from activated platelets. An abn ormal platelet activity has been reported in patients with ulcerative colit is (UC) and Crohn's disease (CD), jointly referred to as inflammatory bowel disease (IBD), which could have an aggravating influence on the inflammato ry response. In addition, an upregulation of platelet IL receptors among pa tients with IBD has been reported. To reveal a presumptuous platelet dysfun ction we analysed the expression of platelet surface P-selectin at resting state and after stimulation with thrombin, collagen, epinephrine and interl eukin 8 (IL-8), and plasma levels of soluble P-selectin, neuropeptide Y (NP Y) and RANTES in patients with IBD. Subjects: Blood from twelve healthy subjects (control group) and twenty-one patients with IBD who had not taken any anti-platelet drugs or steroids we re analysed. Methods. Patients were sub-grouped according to disease entity, disease act ivity and 5ASA medication. Surface P-selectin expression on isolated human platelets and plasma P-selectin, NPY and RANTES were analysed with ELISA. A ll values are presented as mean +/- standard error of the mean (SEM). Mann- Whitney U test and Wilcoxon matched rank test were used for statistical ana lyses. Results: Patients with IBD in remission (n = 9) had higher basal P-selectin expression, 0.38 +/- 0.04, compared to the control group (n = 12), 0.22 +/ - 0.03, p < 0.01. UC patients (n = 16) showed down-regulation of P-selectin expression after stimulation with IL-8, 0.26 +/- 0.03 to 0.22 +/- 0.021 p < 0.05. No significant differences could be observed concerning soluble P-s electin and NPY in plasma. Patients with 5ASA (n = 12) had lower levels of plasma RANTES, 2.39 +/- 0.06 mu g/l, compared to the control group (n = 12) , 3.29 +/- 0.19 mu g/l, p < 0.01, and patients without 5ASA (n = 9), 2.90 /- 0.17 mu g/l, p < 0.05. Conclusions: Patients with IBD in remission have higher basal platelet surf ace P-selectin expression, An exaggerated platelet activity with increased expression of platelet P-selectin and release of inflammatory mediators suc h as RANTES, which is chemotactic and induce chemokine production, could ha ve a reinforcing and aggravating influence on the inflammatory response and increase the susceptibility to IBD. In addition IL-8 has a down-regulating effect on platelet surface P-selectin expression and 5ASA medication seems to lower plasma RANTES. If 5ASA is responsible for lowering the concentrat ion of RANTES this could be one of the beneficial outcomes of 5ASA medicati on.