Mast cells are required for experimental oral allergen–induced diarrhea

Abstract

Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: 5-hydroxytryptamine (5-HT); mucosal mast cell proteases-1-9 (MMCP-1-9); platelet-activating factor (PAF); ribonuclease protection assay (RPA); anti-IgE Ab (EM-95); major basic protein (MBP); anti-c-kit Ab (ACK2). 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. Mast cells are required for experimental oral allergen-induced diarrhea

Recombinant Soybean Protein β-Conglycinin α′-Subunit Expression and Induced Hypersensitivity Reaction in Rats

“…In the present study, the total serum IgE and α′-subunit-specific IgE and IgG1 levels increased after oral sensitization. The intestinal damage and diarrhea could have been caused by antibody-mediated immune reaction to antigen [18, 27]. Damaged villus and the occurrence of diarrhea in our study coincided with a rise in α′-subunit-specific IgE and IgG1 antibody levels.…”

“…Histamine may be one important mediator, as humans and animals with food allergy show elevated histamine release from the gastric and intestinal mucosa following antigen challenge [44]. An increase in histamine levels is widely known as one symptom of mast cell degranulation [27]. The occurrence of a food-allergic reaction depends on the release of histamine and other inflammatory mediators after IgE antibodies on the surface of the mast cells bind to the allergen.…”

“…Histamine brings into play secretory, contractile and immune effects on the intestine. Brandt et al [27 ]reported that mast cells and histamine were responsible for allergen-induced diarrhea. Consistent with this report, we found that dietary supplementation with α′-subunit induced diarrhea in some rats.…”

“…Levels of β-conglycinin α′-subunit-specific IgE and IgG1 antibodies were measured by indirect sandwich ELISA following the procedures described by Brandt et al [27] with slight modifications. Briefly, 96-well microplates (BioFil, Canada) were coated with 20 µg/ml β-conglycinin α′-subunit in carbonate buffer (0.05 M , pH 9.6), and then serial dilutions of serum obtained from experimental rats (100 µl/well) were added and incubated.…”

Therapeutic Effect of Kakkonto in a Mouse Model of Food Allergy with Gastrointestinal Symptoms

“…All mice were housed in the experimental animal facility of the University of Toyama. The experimental methods employed were modified from previous reports [8, 9, 27]. Mice were sensitized twice at 2-week intervals by intraperitoneal injection of 50 µg of OVA (fraction V; Sigma, St. Louis, Mo., USA) in the presence of 1.3 mg of aluminum hydroxide gel (Sigma) as an adjuvant.…”