Mast cells to blame for allergic diarrhea

December 04, 2003

While exposure to food allergens is often associated with diarrhea in humans, knowledge of the cell types and mediators involved in the process is still limited.

A report from Marc Rothenberg and colleagues from Cincinnati Children's Hospital Medical Center, Ohio, in the December 4 issue of the Journal of Clinical Investigation describes the use of a murine model of oral allergen-induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses.

Mice had dose-dependent acute diarrhea associated with increased intestinal permeability, and an increase in granular white blood cells (eosinophilia) and mast cells (mastocytosis). Depletion of mast cells completely abrogated intestinal mastocytosis and blocked the allergic diarrhea.

Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. Additional experiments indicated that the numerous eosinophils present in the intestines did not contribute to the diarrhea.

These results demonstrate that oral allergen-induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, serotonin, and PAF dependent. The identified mechanism also suggests that agents such as anti-IgE, recently approved for the treatment of human asthma, and the c-kit inhibitor imatinib mesilate, recently approved for the treatment of various malignancies, may also have therapeutic utility for gastrointestinal allergy.
TITLE: Mast cells are required for experimental oral allergen-induced diarrhea

Marc E. Rothenberg
Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA
Phone: 513-636-7210
Fax: 513-636-3310

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JCI Journals

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