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

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.

• Authors: B K Wershil, I Castagliuolo, C Pothoulakis
• Journal: Gastroenterology (Gastroenterology) Vol. 114 Issue 5 Pg. 956-64 (May 1998) ISSN: 0016-5085 [Print] United States
• PMID: 9558284 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

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

Topics

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