Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Toxins*
  • Biphenyl Compounds / pharmacology
  • Body Fluids / metabolism
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Enteritis / chemically induced*
  • Enteritis / metabolism
  • Enterotoxins*
  • Intestinal Mucosa / metabolism
  • Male
  • Mast Cells / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains / metabolism
  • Neurokinin-1 Receptor Antagonists
  • Neutrophils / drug effects
  • Neutrophils / physiology
  • Reference Values


  • Bacterial Toxins
  • Biphenyl Compounds
  • Enterotoxins
  • Neurokinin-1 Receptor Antagonists
  • tcdA protein, Clostridium difficile
  • CP 96345