Abstract
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 (ΔI(sc)) that was antigen-specific and inhibited by furosemide. Colonic segments from infected, mast cell-deficient W/W(v) 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 ΔI(sc) 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 ΔI(sc) in the jejunum or on Cl- secretagogue-stimulated ΔI(sc) 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. Furthermore, dietary aspirin has differential effects on immune-mediated ion transport of the distal colon and jejunum, suggesting that mucosal immune function at different sites can be preferentially targeted for pharmacological modulation.
Original language | English (US) |
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Pages (from-to) | 135-142 |
Number of pages | 8 |
Journal | International Archives of Allergy and Immunology |
Volume | 105 |
Issue number | 2 |
DOIs | |
State | Published - 1994 |
Keywords
- Aspirin
- Colon
- Leukotrienes
- Mast cell
- Mucosal immunity
- Prostaglandins
- Trichinella spiralis
- Ussing chamber
- W/W(v) mice
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology