Intestinal mast cells are increased in a mouse model of eosinophilic gastroenteritis following oral allergen challenge

Abstract

Rationale Eosinophilic gastroenteritis (EG) is a disease with a poorly understood pathophysiology. Evidence suggests a Th2 mediated allergy to foods. Since mast cells are implicated in immediate hypersensitivity gut reactions, we were interested in examining their participation in EG. Methods 3 week-old BALB/c mice were divided into 3 groups: One group was sensitized by i.p. injection with OVA/alum and then orally challenged twice with soluble OVA [sens/chal]. The second group was only sensitized [sens only] and the third was only challenged [chal only]. Serum OVA specific IgG1 and IgE concentrations were determined by ELISA. IL-4, IL-5 and IFN-γ levels were determined in the supernatants from OVA stimulated splenocyte cultures using ELISA. Jejunal sections were examined for eosinophils by immunohistochemical staining for MBP, and for mast cells by toluidine blue staining. Results Mice in the sens/chal group displayed a Th2 profile, as evidenced by elevated serum IgG1 and IgE, elevated IL-4 and IL-5 and decreased IFN-γ levels in splenocyte supernatants. Histologically, mice in the sens/chal group had more mast cells than the chal only and the sens only groups [35.1 ± 7.6 mast cells/HPF versus 19.0 ± 4.3, p=0.05 and 14.1 ± 5.5, p<0.05 respectively]. This increase paralleled that of the eosinophils [39.7 ± 1.9 eosinophils/HPF versus 16.2 ± 0.4 and 14.0 ± 3.2 respectively]. Numerous mast cells were invading the surface epithelium. Conclusions Oral allergen challenge induced a marked increase in intestinal mast cells in a mouse model of EG. Many were intraepithelial, indicating a possible role of mast cells in the pathophysiology of EG. The model will be used to examine mechanisms underlying this finding.