An etiological role for aeroallergens and eosinophils in experimental esophagitis.
Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.
Mishra
A
A
Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Hogan
S P
SP
Brandt
E B
EB
Rothenberg
M E
ME
D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D004941:Esophagitis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron
D000485:Allergens; D015848:Interleukin-5