A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation.
Although eosinophils have been implicated in the pathogenesis of gastrointestinal disorders, their function has not been established. Using a murine model of oral antigen-induced eosinophil-associated gastrointestinal disease, we report the pathological consequences of eosinophilic inflammation and the involvement of eotaxin and eosinophils. Exposure of mice to enteric-coated antigen promotes an extensive T helper 2-associated eosinophilic inflammatory response involving the esophagus, stomach, small intestine and Peyer's patches as well as the development of gastric dysmotility, gastromegaly and cachexia. Electron microscopy shows eosinophils in proximity to damaged axons, which indicated that eosinophils were mediating a pathologic response. In addition, mice deficient in eotaxin have impaired eosinophil recruitment and are protected from gastromegaly and cachexia. These results establish a critical pathological function for eotaxin and eosinophils in gastrointestinal allergic hypersensitivity.
Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
S P
SP
Hogan
A
A
Mishra
E B
EB
Brandt
M P
MP
Royalty
S M
SM
Pope
N
N
Zimmermann
P S
PS
Foster
M E
ME
Rothenberg
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology / Q000473:pathology; D004804:Eosinophils / Q000276:immunology* / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018418:Th2 Cells / Q000276:immunology / Q000473:pathology
D000941:Antigens; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines