Mast cells are required for experimental oral allergen–induced diarrhea
Eric B. Brandt, … , Fred D. Finkelman, Marc E. Rothenberg
Eric B. Brandt, … , Fred D. Finkelman, Marc E. Rothenberg
Published December 1, 2003
Citation Information: J Clin Invest. 2003;112(11):1666-1677. https://doi.org/10.1172/JCI19785.
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Article Immunology

Mast cells are required for experimental oral allergen–induced diarrhea

Abstract

Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen–induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum–sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti–c-kit mAb), anti-IgE treatment, and FcεRI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen–induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.

Authors

Eric B. Brandt, Richard T. Strait, Dan Hershko, Quan Wang, Emily E. Muntel, Troy A. Scribner, Nives Zimmermann, Fred D. Finkelman, Marc E. Rothenberg

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Figure 1

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A murine model of allergen-induced diarrhea. (a) The time line illustrat...
A murine model of allergen-induced diarrhea. (a) The time line illustrates that mice were sensitized with two OVA/alum intraperitoneal (i.p.) injections (vertical hatch mark) and subsequently treated with intragastric (i.g.) saline or OVA challenges every 2–3 days (vertical lines). (b) Diarrhea occurrence was assessed 15–45 minutes after intragastric challenges with either saline or increasing doses of OVA (2–50 mg in 250 μl of saline). (c) Diarrhea occurrence in BALB/c mice (n = 16) was compared with C57Bl/6 mice (n = 8) following ten intragastric OVA challenges (50 mg). (d) Representative photograph of the cecum and colon of BALB/c mice 60 minutes after ten intragastric saline or OVA challenges (upper and lower two samples, respectively). (e) Nonsensitized mice (n = 8) or OVA/alum–sensitized mice (n = 15) were treated with repeated doses of intragastric OVA (50 mg). Following five doses of OVA, sensitized mice were challenged with BSA (50 mg) as a control before resuming OVA challenges.