Danese S, Katz J A, Saibeni S, Papa A, Gasbarrini A, Vecchi M, Fiocchi C
Division of Gastroenterology, University Hospitals of Cleveland, Case Western Reserve University School of Medicine Cleveland, Ohio 44106-4952, USA.
Gut. 2003 Oct;52(10):1435-41. doi: 10.1136/gut.52.10.1435.
The CD40/CD40L system, a key regulator and amplifier of immune reactivity, is activated in inflammatory bowel disease (IBD) mucosa.
To determine whether plasma levels of sCD40L are elevated in Crohn's disease (CD) and ulcerative colitis (UC) patients compared with normal controls, to investigate the cellular source of sCD40L, and to explore CD40L induction mechanisms.
CD, UC, and normal control subjects were studied.
The concentration of sCD40L in plasma and supernatants of freshly isolated platelets and autologous peripheral blood T cells (PBT) was measured by ELISA. Surface CD40L expression level was measured by flow cytometry in resting and thrombin activated platelets, and unstimulated and CD3/CD28 stimulated PBT before and after coculture with human intestinal microvascular endothelial cells (HIMEC).
Compared with normal controls, plasma sCD40L levels were significantly higher in both CD and UC patients and proportional to the extent of mucosal inflammation. Platelets from IBD patients displayed a significantly higher surface CD40L expression than those from control subjects, and released greater amounts of sCD40L than autologous PBT. Contact with IL-1beta activated HIMEC induced significant upregulation of CD40L surface expression and release by platelets.
Elevated levels of sCD40L in the circulation of IBD patients reflect enhanced surface expression and release of CD40L by platelets. This phenomenon translates to an increased platelet activation state apparently induced by passage through an inflamed mucosal microvascular bed, a conclusion supported by the positive correlation of plasma sCD40L levels with the extent of anatomical involvement by IBD. These results suggest that platelet-endothelial interactions critically contribute to activation of the CD40 pathway in IBD.
CD40/CD40L系统是免疫反应的关键调节和放大因子，在炎症性肠病（IBD）黏膜中被激活。
确定与正常对照相比，克罗恩病（CD）和溃疡性结肠炎（UC）患者血浆中可溶性CD40L（sCD40L）水平是否升高，研究sCD40L的细胞来源，并探讨CD40L的诱导机制。
研究了CD、UC和正常对照受试者。
采用酶联免疫吸附测定法（ELISA）检测新鲜分离血小板和自体外周血T细胞（PBT）血浆及上清液中sCD40L的浓度。采用流式细胞术检测静息和凝血酶激活血小板以及未刺激和CD3/CD28刺激的PBT与人肠道微血管内皮细胞（HIMEC）共培养前后表面CD40L的表达水平。
与正常对照相比，CD和UC患者血浆sCD40L水平均显著升高，且与黏膜炎症程度成正比。IBD患者的血小板表面CD40L表达明显高于对照受试者，释放的sCD40L量也多于自体PBT。与白细胞介素-1β激活的HIMEC接触可显著上调血小板表面CD40L的表达并促进其释放。
IBD患者循环中sCD40L水平升高反映了血小板表面CD40L表达增强和释放增加。这一现象表明血小板激活状态增加，显然是由通过炎症黏膜微血管床所致，血浆sCD40L水平与IBD解剖学累及范围的正相关支持了这一结论。这些结果表明，血小板-内皮细胞相互作用对IBD中CD40途径的激活起关键作用。
