Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease
Phagocyte-specific S100 proteins are released from affected mucosa and promote immune responses during inflammatory bowel disease
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DOI：
10.1002/path.2394
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发表时间：
2008-10-01
影响因子：
7.3
通讯作者：
Clancy, R.
中科院分区：
文献类型：
--
作者：
Foell, D.;Wittkowski, H.;Clancy, R.
吞噬细胞衍生的S100蛋白是先天免疫反应的内源性激活剂。S100A12与晚期糖基化终产物受体结合，而S100A8/S100A9复合物（髓细胞相关蛋白，MRP8/14；钙保护蛋白）是toll样的配体。这些S100蛋白可以在粪便中检测到。在本研究中，我们分析了肠组织中的S100A12和MRP8/14。内镜检查时采集克罗恩病（CD, n = 30）、溃疡性结肠炎（UC, n = 30）、肠易激综合征（IBS, n = 30）或无炎症（n = 30）患者标本。培养24 h后，在上清液中分析S100A12和MRP8/14。内镜、组织学、实验室和临床疾病活动度测量均被记录。我们发现炎症性肠病（IBD）组织中S100A12的自发释放增加。与非炎症组织相比，炎症组织中S100A12在上清液中的释放量增加了28倍（平均46.9 vs. 1.7 ng/ml, p < 0.0001）。在活动性CD中，S100A12和MRP8/14的释放强烈依赖于定位，与结肠炎症相比，活动性回肠炎症部位的释放很少。与MRP8/14相比，S100A12的这种差异更为明显。S100A12和MRP8/14诱导正常结肠组织分离的人肠道微血管内皮细胞（HIMECs）黏附分子和趋化因子上调。吞噬细胞来源的S100蛋白从炎症组织中直接释放可能反映浸润性中性粒细胞（S100A12）以及单核细胞或上皮细胞（MRP8/14）的分泌。通过激活模式识别受体，这些蛋白质促进肠道组织的炎症。增强的粘膜释放可以解释IBD中粪便标志物与疾病活动性的相关性。版权所有2008年英国和爱尔兰病理学会。约翰·威利父子有限公司出版。
Phagocyte-derived S100 proteins are endogenous activators of innate immune responses. S100A12 binds to the receptor for advanced glycation end-products, while complexes of S100A8/S100A9 (myeloid-related proteins, MRP8/14; calprotectin) are ligands of toll-like These S100 proteins can be detected in stool. In the present study we analyse of S100A12 and MRP8/14 from intestinal tissue. Specimens from patients with Crohn's disease (CD; n = 30), ulcerative colitis (UC; n = 30), irritable bowel syndrome (IBS; n = 30) or without inflammation (n = 30) were obtained during endoscopy. After 24 h culture, S100A12 and MRP8/14 were analysed in supernatants. Endoscopic, histological, laboratory and clinical disease activity measures were documented. We found an increased spontaneous release of S100A12 from tissue in inflammatory bowel disease (IBD). The release of S100A12 into the supernatants was 28-fold enhanced in inflamed tissue when compared to non-inflamed tissue (mean 46.9 vs. 1.7 ng/ml, p < 0.0001). In active CD, release of S100A12 and MRP8/14 was strongly dependent on localization, with little release from sites of active ileal inflammation compared to colonic inflammation. This difference was more pronounced for S100A12 than for MRP8/14. S100A12 and MRP8/14 provoked up-regulation of adhesion molecules and chemokines on human intestinal microvascular endothelial cells (HIMECs) isolated from normal colonic tissue. The direct release of phagocyte-derived S100 proteins from inflamed tissues may reflect secretion from infiltrating neutrophils (S100A12) and also monocytes or epithelial cells (MRP8/14). Via activation of pattern recognition receptors, these proteins promote inflammation in intestinal tissue. The enhanced mucosal release can explain the correlation of fecal markers with disease activity in IBD). Copyright (C) 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.