Murine model of food allergy after epicutaneous sensitization: role of mucosal mast cell protease-1.
OBJECTIVE
Studies of the pathological mechanisms of food allergy have been impeded by the lack of relevant animal models. The purpose of this study was to develop a physiological model of food allergy that was not dependent on immunostimulatory adjuvants.


METHODS
Balb/c mice were epicutaneously sensitized four times at varying intervals over a 22-day period, and challenged orally from day 40, 6 times every 1-3 days with either saline or ovalbumin.


RESULTS
After sensitization (day 35) but before the oral challenges, the ovalbumin-sensitized groups showed increased specific IgE and IgG1 production when compared with the sham-sensitized groups. Mucosal mast cell protease-1 (MMCP-1) was undetectable in serum before the intragastric challenge. MMCP-1 concentrations were increased after the first ovalbumin dose, solely in the ovalbumin-sensitized and -challenged group. After the challenge period, the mean serum MMCP-1 concentration increased from an undetectable level in controls to an over 44-fold level in the ovalbumin-sensitized and -challenged mice. In this group, MMCP-1-positive cells were present in the small intestine and expressions of IFN-gamma and CXCL-9 mRNA were decreased in the ileum, suggesting an impaired Th-1-type response. Within one hour of the last ovalbumin challenge, 5 out of 6 mice developed diarrhea in the ovalbumin-sensitized and -challenged group, but there was no diarrhea in the other groups.


CONCLUSIONS
A murine model of food allergy based on sensitization via epicutaneous exposure to allergen without immunostimulatory adjuvants was developed. Effective production of MMCP-1 together with specific IgE and IgG1 suggests a breakdown in oral tolerance to the allergen. Intragastric challenges were accompanied by mast cell-dependent immunopathological changes and diarrhea.
Vaali
Kirsi
K
Department of Viral Diseases and Immunology, Laboratory of Immunology, National Public Health Institute, Helsinki, Finland. kirsi.vaali@ktl.fi
Puumalainen
Tuija J
TJ
Lehto
Maili
M
Wolff
Henrik
H
Rita
Hannu
H
Alenius
Harri
H
Palosuo
Timo
T
D000818:Animals; D053818:Chymases / Q000097:blood / Q000502:physiology*; D003967:Diarrhea / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology
D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D053818:Chymases; C509230:Mcpt1 protein, mouse