Direct evidence of mast cell involvement in Clostridium difficile toxin a—induced enteritis in mice

BK Wershil, I Castagliuolo, C Pothoulakis - Gastroenterology, 1998 - Elsevier
BK Wershil, I Castagliuolo, C Pothoulakis
Gastroenterology, 1998Elsevier
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 …
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. GASTROENTEROLOGY 1998;114:956-964
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