Fägerstam J P, Whiss P A, Ström M, Andersson R G
University of Linköping, Department of Medicine and Care, Faculty of Health Sciences, Sweden.
Inflamm Res. 2000 Sep;49(9):466-72. doi: 10.1007/s000110050618.
P-selectin, a membrane glycoprotein which is expressed on activated platelets and endothelial cells, plays a crucial role in the inflammatory response. The main action is adhesion of leukocytes, facilitation of diapedesis and induction of cytokine production from monocytes (MCP-1 and IL-8), mediated via RANTES released from activated platelets. An abnormal platelet activity has been reported in patients with ulcerative colitis (UC) and Crohn's disease (CD), jointly referred to as inflammatory bowel disease (IBD), which could have an aggravating influence on the inflammatory response. In addition, an up-regulation of platelet IL-8 receptors among patients with IBD has been reported. To reveal a presumptuous platelet dysfunction we analysed the expression of platelet surface P-selectin at resting state and after stimulation with thrombin, collagen, epinephrine and interleukin 8 (IL-8), and plasma levels of soluble P-selectin, neuropeptide Y (NPY) and RANTES in patients with IBD.
Blood from twelve healthy subjects (control group) and twenty-one patients with IBD who had not taken any anti-platelet drugs or steroids were analysed.
Patients were sub-grouped according to disease entity, disease activity and 5ASA medication. Surface P-selectin expression on isolated human platelets and plasma P-selectin, NPY and RANTES were analysed with ELISA. All values are presented as mean +/- standard error of the mean (SEM). Mann-Whitney U test and Wilcoxon matched rank test were used for statistical analyses.
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+/-0.02, p < 0.05. No significant differences could be observed concerning soluble P-selectin and NPY in plasma. Patients with 5ASA (n = 12) had lower levels of plasma RANTES, 2.39+/-0.06 microg/l, compared to the control group (n = 12), 3.29+/-0.19 microg/l, p < 0.01, and patients without 5ASA (n = 9), 2.90+/-0.17 microg/l, p < 0.05.
Patients with IBD in remission have higher basal platelet surface P-selectin expression. An exaggerated platelet activity with increased expression of platelet P-selectin and release of inflammatory mediators such as RANTES, which is chemotactic and induce chemokine production, could have 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 concentration of RANTES this could be one of the beneficial outcomes of 5ASA medication.
P-选择素是一种在活化血小板和内皮细胞上表达的膜糖蛋白，在炎症反应中起关键作用。其主要作用是介导白细胞黏附、促进白细胞渗出以及诱导单核细胞产生细胞因子（单核细胞趋化蛋白-1和白细胞介素-8），这一过程通过活化血小板释放的调节激活正常T细胞表达和分泌的趋化因子来实现。据报道，溃疡性结肠炎（UC）和克罗恩病（CD）患者（统称为炎症性肠病，IBD）存在血小板活性异常，这可能会加重炎症反应。此外，有报道称IBD患者血小板白细胞介素-8受体上调。为揭示可能存在的血小板功能障碍，我们分析了IBD患者静息状态下以及用凝血酶、胶原蛋白、肾上腺素和白细胞介素-8（IL-8）刺激后血小板表面P-选择素的表达，以及血浆中可溶性P-选择素、神经肽Y（NPY）和调节激活正常T细胞表达和分泌的趋化因子的水平。
分析了12名健康受试者（对照组）以及21名未服用任何抗血小板药物或类固醇的IBD患者的血液。
根据疾病类型、疾病活动度和5-氨基水杨酸（5ASA）用药情况对患者进行分组。用酶联免疫吸附测定法（ELISA）分析分离出的人血小板表面P-选择素表达以及血浆中的P-选择素、NPY和调节激活正常T细胞表达和分泌的趋化因子。所有数值均以平均值±平均标准误差（SEM）表示。采用曼-惠特尼U检验和威尔科克森配对秩和检验进行统计分析。
缓解期IBD患者（n = 9）的基础P-选择素表达水平为0.38±0.04，高于对照组（n = 12）的0.22±0.03，p < 0.01。UC患者（n = 16）在用IL-8刺激后P-选择素表达下调，从0.26±0.03降至0.22±0.02，p < 0.05。血浆中可溶性P-选择素和NPY未观察到显著差异。服用5ASA的患者（n = 12）血浆调节激活正常T细胞表达和分泌的趋化因子水平为2.39±0.06微克/升，低于对照组（n = 12）的3.29±0.19微克/升，p < 0.01，也低于未服用5ASA的患者（n = 9）的2.90±0.17微克/升，p < 0.05。
缓解期IBD患者血小板表面基础P-选择素表达较高。血小板活性增强，表现为血小板P-选择素表达增加以及释放如调节激活正常T细胞表达和分泌的趋化因子等炎症介质，这可能会增强和加重炎症反应，并增加对IBD的易感性。此外，IL-8对血小板表面P-选择素表达有下调作用，5ASA用药似乎会降低血浆调节激活正常T细胞表达和分泌的趋化因子水平。如果5ASA是导致调节激活正常T细胞表达和分泌的趋化因子浓度降低的原因，这可能是5ASA用药的有益效果之一。
