Castagliuolo I, Riegler M, Pasha A, Nikulasson S, Lu B, Gerard C, Gerard N P, Pothoulakis C
Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Clin Invest. 1998 Apr 15;101(8):1547-50. doi: 10.1172/JCI2039.
Toxin A, a 308,000-Mr enterotoxin from Clostridium difficile, mediates antibiotic-associated diarrhea and colitis in humans. Injection of toxin A into animal intestine triggers an acute inflammatory response characterized by activation of sensory neurons and immune cells of the intestinal lamina propria, including mast cells and macrophages, and migration of circulating neutrophils in the involved intestinal segment. In this study we show that mice genetically deficient in the neurokinin-1 receptor are protected from the secretory and inflammatory changes as well as from epithelial cell damage induced by toxin A. The protective effect of neurokinin-1R deletion correlates with diminished intestinal levels of the cytokine TNF-alpha and its mRNA and the leukocyte enzyme myeloperoxidase. These results demonstrate a major requirement for substance P receptors in the pathogenesis of acute inflammatory diarrhea.
毒素A是一种来自艰难梭菌的分子量为308,000的肠毒素，可介导人类抗生素相关性腹泻和结肠炎。将毒素A注入动物肠道会引发急性炎症反应，其特征是感觉神经元和肠固有层免疫细胞（包括肥大细胞和巨噬细胞）的激活，以及受累肠段循环中性粒细胞的迁移。在本研究中，我们发现神经激肽-1受体基因缺陷的小鼠可免受毒素A诱导的分泌和炎症变化以及上皮细胞损伤。神经激肽-1受体缺失的保护作用与肠道中细胞因子肿瘤坏死因子-α及其mRNA水平以及白细胞酶髓过氧化物酶的降低相关。这些结果表明，P物质受体在急性炎症性腹泻的发病机制中起主要作用。
