Mast cell-dependent tumor necrosis factor alpha production participates in allergic gastric inflammation in mice.
OBJECTIVE
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)-alpha participates in the recruitment of neutrophils during this response.


METHODS
The levels of TNF-alpha 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-alpha transcripts. Anti-TNF-alpha antibodies or cyclosporine A were used in an attempt to inhibit neutrophil infiltration.


RESULTS
TNF-alpha mRNA and protein were increased in gastric tissues undergoing immunoglobulin E-dependent inflammation. Mast cells were required for the development of cells expressing TNF-alpha transcripts in the stomach. Seventy-nine percent of the cells in the mucosa and 100% of the cells in the submucosa expressing TNF-alpha mRNA were identified as mast cells. Anti-TNF-alpha antibodies inhibited neutrophil infiltration in the submucosa, and cyclosporine A inhibited the tissue expression of TNF-alpha mRNA and the influx of neutrophils into the submucosa and muscularis propria.


CONCLUSIONS
These findings show that mast cell-derived TNF-alpha is at least one of the mediators involved in the recruitment of neutrophils during immunoglobulin E-dependent gastric inflammation in the mouse.
Furuta
G T
GT
Combined Program in Pediatric Gastroenterology and Nutrition, Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Schmidt-Choudhury
A
A
Wang
M Y
MY
Wang
Z S
ZS
Lu
L
L
Furlano
R I
RI
Wershil
B K
BK
D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology; D005756:Gastritis / Q000209:etiology*; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007073:Immunoglobulin E; D016572:Cyclosporine