Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy.
Penetration of the gut epithelial barrier by intact luminal antigen is necessary for immunologically mediated pathophysiology in the context of food allergy. We investigated if glucagon-like peptide-2 (GLP-2) could affect immediate hypersensitivity and late-phase allergic inflammation in a murine model. Mice were sensitized to horseradish peroxidase (HRP); studies were conducted 14 days later. Mice were treated with 5 microg GLP-2 subcutaneously 4 h before antigen challenge. For immediate hypersensitivity, jejunal segments in Ussing chambers were challenged by luminal HRP antigen. GLP-2 treatment reduced the uptake of HRP and the antigen-induced secretory response after luminal challenge. GLP-2 appears to reduce macromolecular uptake independent of the CD23-mediated enhanced antigen uptake pathway. For the late phase, mice were gavaged with antigen, and 48 h later the function and histology of the jejunum were examined. GLP-2 prevented the usual prolonged permeability defect and reduced the number of inflammatory cells in the mucosa. Our studies demonstrate that a single treatment of sensitized mice with GLP diminishes both immediate and late-phase hypersensitivity reactions characteristic of food allergy by inhibiting transepithelial uptake of antigen.
Intestinal Disease Research Programme, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
Heather L
HL
Cameron
Ping-Chang
PC
Yang
Mary H
MH
Perdue
D000818:Animals; D002463:Cell Membrane Permeability; D004195:Disease Models, Animal; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005512:Food Hypersensitivity / Q000276:immunology* / Q000503:physiopathology*; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006735:Horseradish Peroxidase / Q000276:immunology / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000494:pharmacology*
D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides; D006735:Horseradish Peroxidase