Background and Aims: Immunoglobulin E-dependent gastric inflammation is characterized by neutrophil infiltration, and mast cells are required for this response. The aim of this study was to examine whether mast cell production of tumor necrosis factor (TNF)-α participates in the recruitment of neutrophils during this response. Methods: The levels of TNF-α messenger RNA (mRNA) and protein in gastric tissues were assessed by Northern blot analysis and enzyme-linked immunosorbent assay. In situ hybridization and histochemical staining were performed to identify the cells expressing TNF- α transcripts. Anti-TNF-α antibodies or cyclosporine A were used in an attempt to inhibit neutrophil infiltration. Results: TNF-α mRNA and protein were increased in gastric tissues undergoing immunoglobulin E-dependent inflammation. Mast cells were required for the development of cells expressing TNF-α transcripts in the stomach. Seventy-nine percent of the cells in the mucosa and 100% of the cells in the submucosa expressing TNF-α mRNA were identified as mast cells. Anti-TNF-α antibodies inhibited neutrophil infiltration in the submucosa, and cyclosporine A inhibited the tissue expression of TNF-α mRNA and the influx of neutrophils into the submucosa and muscularis propria. Conclusions: These findings show that mast cell-derived TNF-α is at least one of the mediators involved in the recruitment of neutrophils during immunoglobulin E-dependent gastric inflammation in the mouse.
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