Mast cells and gastrointestinal dysmotility in the cystic fibrosis mouse.
BACKGROUND
Cystic fibrosis (CF) has many effects on the gastrointestinal tract and a common problem in this disease is poor nutrition. In the CF mouse there is an innate immune response with a large influx of mast cells into the muscularis externa of the small intestine and gastrointestinal dysmotility. The aim of this study was to evaluate the potential role of mast cells in gastrointestinal dysmotility using the CF mouse (Cftr(tm1UNC), Cftr knockout).


METHODS
Wild type (WT) and CF mice were treated for 3 weeks with mast cell stabilizing drugs (ketotifen, cromolyn, doxantrazole) or were treated acutely with a mast cell activator (compound 48/80). Gastrointestinal transit was measured using gavage of a fluorescent tracer.


RESULTS
In CF mice gastric emptying at 20 min post-gavage did not differ from WT, but was significantly less than in WT at 90 min post-gavage. Gastric emptying was significantly increased in WT mice by doxantrazole, but none of the mast cell stabilizers had any significant effect on gastric emptying in CF mice. Mast cell activation significantly enhanced gastric emptying in WT mice but not in CF mice. Small intestinal transit was significantly less in CF mice as compared to WT. Of the mast cell stabilizers, only doxantrazole significantly affected small intestinal transit in WT mice and none had any effect in CF mice. Mast cell activation resulted in a small but significant increase in small intestinal transit in CF mice but not WT mice.


CONCLUSIONS
The results indicate that mast cells are not involved in gastrointestinal dysmotility but their activation can stimulate small intestinal transit in cystic fibrosis.
De Lisle
Robert C
RC
Anatomy & Cell Biology, University of Kansas School of Medicine, Kansas City, Kansas, United States of America. rdelisle@kumc.edu
Meldi
Lauren
L
Roach
Eileen
E
Flynn
Maureen
M
Sewell
Racquel
R
D000818:Animals; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004195:Disease Models, Animal; D005746:Gastric Emptying / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000473:pathology; D005772:Gastrointestinal Transit / Q000502:physiology*; D007113:Immunity, Innate; D007421:Intestine, Small / Q000473:pathology; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013892:Thioxanthenes / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology
D013892:Thioxanthenes; D044004:Xanthones; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C010134:doxantrazole