Wershil B K, Castagliuolo I, Pothoulakis C
Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital and Massachusetts General Hospital, Boston, Massachusetts, USA.
Gastroenterology. 1998 May;114(5):956-64. doi: 10.1016/s0016-5085(98)70315-4.
BACKGROUND & AIMS: The pathogenesis of Clostridium difficile toxin A-induced intestinal inflammation is not completely understood. The aim of this study was to define the contribution of mast cells to the fluid secretion and neutrophil infiltration associated with toxin A-induced enteritis.
Fluid secretion and neutrophil infiltration in toxin A- or buffer-challenged ileal loops were assessed in normal, mast cell-deficient, and mast cell-deficient KitW/KitW-v mice that had undergone selective repair of their mast cell deficiency. The effect of a specific substance P-receptor antagonist was also studied.
Intestinal fluid secretion and neutrophil recruitment were significantly diminished in mast cell-deficient KitW/KitW-v and mast cell-deficient MgfSl/MgfSl-d mice compared with the respective normal mice. Mast cell-reconstituted KitW/KitW-v mice showed responses similar to the normal congenic mice. Administration of a specific substance P-receptor antagonist (CP-96,345) reduced toxin A-induced intestinal fluid secretion and inhibited neutrophil infiltration in normal, mast cell-deficient KitW/KitW-v, and mast cell-reconstituted KitW/KitW-v mice.
C. difficile toxin A elicits intestinal fluid secretion and neutrophil infiltration by both mast cell-dependent and -independent pathways, and substance P participates in both pathways.
艰难梭菌毒素A诱导的肠道炎症发病机制尚未完全明确。本研究旨在明确肥大细胞在毒素A诱导的肠炎相关的液体分泌和中性粒细胞浸润中的作用。
在正常、肥大细胞缺陷及肥大细胞缺陷已选择性修复的KitW/KitW-v小鼠中，评估毒素A或缓冲液刺激回肠肠袢后的液体分泌和中性粒细胞浸润情况。还研究了一种特异性P物质受体拮抗剂的作用。
与各自的正常小鼠相比，肥大细胞缺陷的KitW/KitW-v小鼠和肥大细胞缺陷的MgfSl/MgfSl-d小鼠的肠道液体分泌和中性粒细胞募集显著减少。肥大细胞重建的KitW/KitW-v小鼠表现出与正常同基因小鼠相似的反应。给予特异性P物质受体拮抗剂（CP-96,345）可减少毒素A诱导的正常、肥大细胞缺陷的KitW/KitW-v及肥大细胞重建的KitW/KitW-v小鼠的肠道液体分泌，并抑制中性粒细胞浸润。
艰难梭菌毒素A通过肥大细胞依赖和非依赖途径引发肠道液体分泌和中性粒细胞浸润，且P物质参与这两种途径。
