Mast cells are required for experimental oral allergen-induced diarrhea.
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 Fc epsilon RI-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.
Brandt
Eric B
EB
Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA.
Strait
Richard T
RT
Hershko
Dan
D
Wang
Quan
Q
Muntel
Emily E
EE
Scribner
Troy A
TA
Zimmermann
Nives
N
Finkelman
Fred D
FD
Rothenberg
Marc E
ME
D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000209:etiology; D000818:Animals; D053818:Chymases; D003967:Diarrhea / Q000209:etiology*; D004804:Eosinophils / Q000502:physiology; D007073:Immunoglobulin E / Q000276:immunology; D007413:Intestinal Mucosa / Q000378:metabolism; D008407:Mast Cells / Q000502:physiology*; D008415:Mastocytosis / Q000209:etiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D010539:Permeability; D010972:Platelet Activating Factor / Q000502:physiology; D012697:Serine Endopeptidases / Q000097:blood; D012701:Serotonin / Q000502:physiology; D018418:Th2 Cells / Q000502:physiology
D000485:Allergens; D010972:Platelet Activating Factor; D012701:Serotonin; D007073:Immunoglobulin E; D010047:Ovalbumin; D012697:Serine Endopeptidases; D053818:Chymases