A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy.
Despite marked advances in the understanding of allergic responses, the mechanisms regulating gastrointestinal allergy are not very well understood. We have developed a model of antigen-induced eosinophil-associated gastrointestinal allergy and characterized the role of eotaxin and IL-5. Challenge of allergen-sensitized mice with oral allergen, in the form of enteric-coated beads, resulted in marked allergen-specific IgG(1) and IgE, Th(2)-type (IL-4 and IL-5) cytokine production, and eosinophil accumulation in the blood and small intestine. In the genetic absence of eotaxin, a chemokine constitutively expressed in the gastrointestinal tract, eosinophil recruitment into the small intestine was ablated, and these mice developed enhanced eosinophil accumulation in the blood compared with wild-type mice. Interestingly, in the absence of IL-5, allergen challenge promoted partial eosinophil accumulation into the small intestine and a decline in circulating eosinophil levels. Collectively, these results establish that the accumulation of gastrointestinal eosinophils is antigen induced, can occur independent of IL-5, and provides a molecular mechanism to explain the dichotomy between peripheral blood and tissue eosinophilia. Furthermore, eotaxin is identified as a critical regulator of antigen-induced eosinophilic inflammation in the gastrointestinal tract.
Hogan
S P
SP
Division of Pulmonary Medicine, Allergy and Clinical Immunology, Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Mishra
A
A
Brandt
E B
EB
Foster
P S
PS
Rothenberg
M E
ME
D000707:Anaphylaxis / Q000209:etiology; D000818:Animals; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D004804:Eosinophils / Q000502:physiology*; D005260:Female; D005767:Gastrointestinal Diseases / Q000209:etiology*; D006967:Hypersensitivity / Q000209:etiology*; D016023:Integrins / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000032:analysis
C515457:Ccl11 protein, mouse; C515351:Ccr3 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D016023:Integrins; D015848:Interleukin-5; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; C071777:integrin alpha4beta7; D010047:Ovalbumin