B K Wershil1, I Castagliuolo, C Pothoulakis. 1. Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital and Massachusetts General Hospital, Boston, Massachusetts, USA. bwershil@bidmc.harvard.edu
Abstract
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
Authors: David E Reed; Carlos Barajas-Lopez; Graeme Cottrell; Sara Velazquez-Rocha; Olivier Dery; Eileen F Grady; Nigel W Bunnett; Stephen J Vanner Journal: J Physiol Date: 2003-01-24 Impact factor: 5.182
Authors: Graeme S Cottrell; Silvia Amadesi; Stella Pikios; Eric Camerer; J Adam Willardsen; Brett R Murphy; George H Caughey; Paul J Wolters; Shaun R Coughlin; Anders Peterson; Wolfgang Knecht; Charalabos Pothoulakis; Nigel W Bunnett; Eileen F Grady Journal: Gastroenterology Date: 2007-04-13 Impact factor: 22.682