Bischoff S C, Lorentz A, Schwengberg S, Weier G, Raab R, Manns M P
Department of Gastroenterology and Hepatology, Medical School of Hannover, D-30623 Hannover, Germany.
Gut. 1999 May;44(5):643-52. doi: 10.1136/gut.44.5.643.
Several inflammatory disorders of the intestine are characterised by enhanced expression of tumour necrosis factor alpha (TNF-alpha). Monocytes and macrophages have been suggested as a major cellular source of TNF-alpha in human gut, whereas mast cells, although known to be capable of producing TNF-alpha, have been poorly examined in this respect.
To investigate whether human intestinal mast cells can produce TNF-alpha, and which factors regulate TNF-alpha production in these cells.
Mast cells were isolated from surgery tissue specimens of patients undergoing bowel resection because of cancer. Immunohistochemical studies were performed in biopsy specimens derived from 13 patients (two healthy controls, four with Crohn's disease, four with ulcerative colitis, three others). TNF-alpha mRNA and protein expression were studied in vitro by polymerase chain reaction, RNAse protection assay, western blot, and enzyme linked immunosorbent assay in isolated purified human intestinal mast cells stimulated by IgE receptor crosslinking, intestinal bacteria, and lipopolysaccharide. Cellular localisation of TNF-alpha was examined by immunohistochemistry.
TNF-alpha mRNA and protein were expressed constitutively in isolated human intestinal mast cells. Expression of TNF-alpha mRNA and release of TNF-alpha protein were substantially enhanced by IgE receptor crosslinking and by coculture of mast cells with intestinal bacteria; lipopolysaccharide had only marginal effects. Immunohistochemical studies revealed that approximately 60% of the lamina propria cells with immunoreactivity for TNF-alpha were mast cells.
The data show that mast cells are an important source of TNF-alpha in the human intestinal mucosa.
几种肠道炎症性疾病的特征是肿瘤坏死因子α（TNF-α）表达增强。单核细胞和巨噬细胞被认为是人类肠道中TNF-α的主要细胞来源，而肥大细胞尽管已知能够产生TNF-α，但在这方面的研究较少。
研究人类肠道肥大细胞是否能产生TNF-α，以及哪些因素调节这些细胞中TNF-α的产生。
从因癌症接受肠切除手术的患者的手术组织标本中分离肥大细胞。对13例患者（2例健康对照、4例克罗恩病患者、4例溃疡性结肠炎患者、3例其他患者）的活检标本进行免疫组织化学研究。在体外，通过聚合酶链反应、核糖核酸酶保护测定、蛋白质印迹法和酶联免疫吸附测定，研究分离纯化的人类肠道肥大细胞在受到IgE受体交联、肠道细菌和脂多糖刺激时TNF-α mRNA和蛋白的表达。通过免疫组织化学检查TNF-α的细胞定位。
TNF-α mRNA和蛋白在分离的人类肠道肥大细胞中组成性表达。IgE受体交联以及肥大细胞与肠道细菌共培养可显著增强TNF-α mRNA的表达和TNF-α蛋白的释放；脂多糖的作用很小。免疫组织化学研究显示，对TNF-α有免疫反应性的固有层细胞中约60%是肥大细胞。
数据表明肥大细胞是人类肠道黏膜中TNF-α的重要来源。
