Foell D, Kucharzik T, Kraft M, Vogl T, Sorg C, Domschke W, Roth J
Department of Paediatrics, University of Münster, Germany.
Gut. 2003 Jun;52(6):847-53. doi: 10.1136/gut.52.6.847.
Intestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC) is characterised by an influx of neutrophils into the intestinal mucosa. S100A12 is a calcium binding protein with proinflammatory properties. It is secreted by activated neutrophils and interacts with the multiligand receptor for advanced glycation end products (RAGE). Promising anti-inflammatory effects of blocking agents for RAGE have been reported in murine models of colitis.
To investigate expression and serum concentrations of S100A12 in inflammatory bowel disease (IBD).
We performed immunohistochemical studies and immunofluorescence microscopy in biopsies from patients with CD and UC. S100A12 serum concentrations were analysed using a sandwich ELISA.
Immunohistochemical studies revealed profound expression of S100A12 in inflamed intestinal tissue from IBD patients whereas no expression was found in tissue from healthy controls. Staining for S100A12 during chronic active CD and UC was restricted to infiltrating neutrophils. Serum S100A12 levels were significantly elevated in patients with active CD (470 (125) ng/ml; p<0.001, n=30) as well as those with active UC (400 (120) ng/ml; p<0.01, n=15) compared with healthy controls (75 (15) ng/ml; n=30). Even in inactive disease, elevated serum concentrations were found, at least in CD. S100A12 levels were well correlated with disease activity in CD and UC.
We demonstrated that neutrophil derived S100A12 is strongly upregulated during chronic active IBD, suggesting an important role during the pathogenesis of IBD. Serum S100A12 may serve as a useful marker for disease activity in patients with IBD.
克罗恩病（CD）和溃疡性结肠炎（UC）中的肠道炎症特征为中性粒细胞流入肠道黏膜。S100A12是一种具有促炎特性的钙结合蛋白。它由活化的中性粒细胞分泌，并与晚期糖基化终产物多配体受体（RAGE）相互作用。在结肠炎小鼠模型中，已报道RAGE阻断剂具有有前景的抗炎作用。
研究S100A12在炎症性肠病（IBD）中的表达及血清浓度。
我们对CD和UC患者的活检组织进行了免疫组织化学研究和免疫荧光显微镜检查。使用夹心ELISA分析S100A12血清浓度。
免疫组织化学研究显示，IBD患者炎症肠道组织中S100A12表达显著，而健康对照组织中未发现表达。慢性活动期CD和UC期间S100A12染色仅限于浸润的中性粒细胞。与健康对照（75（15）ng/ml；n = 30）相比，活动期CD患者（470（125）ng/ml；p<0.001，n = 30）以及活动期UC患者（400（120）ng/ml；p<0.01，n = 15）的血清S100A12水平显著升高。即使在非活动期疾病中，至少在CD中也发现血清浓度升高。S100A12水平与CD和UC中的疾病活动密切相关。
我们证明，在慢性活动期IBD期间，中性粒细胞衍生的S100A12强烈上调，提示其在IBD发病机制中起重要作用。血清S100A12可能作为IBD患者疾病活动的有用标志物。
