Mast cell-mediated colonic immune function and its inhibition by dietary aspirin in mice infected with Trichinella spiralis.
Because of the integrated nature of cellular elements in the gut wall, an understanding of the local mucosal immune system and its adaptive capacity should provide more insight into diseases of the colon, such as inflammatory bowel disease and colorectal cancer. To develop a method to quantify colonic mucosal immune function in situ, ion transport mediated by a type I hypersensitivity reaction was measured in the colon of mice infected with Trichinella spiralis. Segments of sensitized distal colon mounted in Ussing chambers and challenged with T. spiralis-derived antigen resulted in a rise in short-circuit current (delta Isc) that was antigen-specific and inhibited by furosemide. Colonic segments from infected, mast cell-deficient W/Wv mice were unresponsive to challenge with T. spiralis antigen. Inhibition of anaphylactic mediators with various pharmacological agents implicated prostaglandins and leukotrienes as the principal mediators of the antigen-induced delta Isc, with 5-HT also playing a role. Neural blockade with tetrodotoxin or blockade of histamine H1 receptors with diphenhydramine failed to inhibit the colonic immune response. Distal colon from immune mice fed an aspirin-containing diet (800 mg/kg powdered diet) ad libitum for 6 weeks had a decreased response to antigen. However, dietary aspirin had no effect on antigen-induced delta Isc in the jejunum or on Cl- secretagogue-stimulated delta Isc in the distal colon. These results suggest that products of arachidonic acid metabolism are important mediators of mast cell-dependent, antigen-stimulated Cl- secretion in the distal colon of mice immunized by infection with T. spiralis.(ABSTRACT TRUNCATED AT 250 WORDS)
Broaddus
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RR
Department of Physiology and Cell Biology, University of Texas Medical School, Houston 77225.
Castro
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GA
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D016718:Arachidonic Acid / Q000502:physiology; D001241:Aspirin / Q000494:pharmacology*; D001679:Biogenic Amines / Q000502:physiology; D003106:Colon / Q000276:immunology* / Q000469:parasitology; D007413:Intestinal Mucosa / Q000276:immunology; D017136:Ion Transport / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000276:immunology* / Q000503:physiopathology
D000947:Antigens, Helminth; D001679:Biogenic Amines; D016718:Arachidonic Acid; D001241:Aspirin