Mast cell activation augments gastric mucosal injury through a leukotriene-dependent mechanism.
Several lines of evidence suggest a role for mast cells as modulators of gastric mucosal integrity, but the effect of antigenic mast cell activation on mucosal resistance to injury has not previously been examined. In this study, rats were sensitized to the nematode Nippostrongylus brasiliensis and were studied 35-42 days later. With use of an ex vivo gastric chamber preparation, the stomach was exposed for 10 min to 20% ethanol. In some rats, antigen was administered intra-arterially 10 min before application of ethanol. Sensitized rats exhibited similar levels of ethanol-induced gastric injury as control rats, despite having significantly greater numbers of mucosal mast cells. However, antigen administration, which did not in itself produce mucosal injury, significantly augmented (approximately 3-fold) the extent of injury in sensitized but not control rats. Prior treatment with dexamethasone depleted mucosal mast cells in control and sensitized rats. Moreover, this treatment abolished the increase in mucosal injury observed in sensitized rats treated with antigen and topical ethanol. Pretreatment with a leukotriene D4-receptor antagonist, but not a platelet-activating factor-receptor antagonist or a cyclooxygenase inhibitor, abolished the increased susceptibility of sensitized rats to gastric damage induced by antigen and topical ethanol. These results suggest that mucosal mast cell number per se does not influence mucosal susceptibility to injury; however, activation of mast cells markedly increases the susceptibility to injury through a peptidoleukotriene-dependent mechanism.
Rioux
K P
KP
Gastrointestinal Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
Wallace
J L
JL
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure; D053818:Chymases; D003907:Dexamethasone / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000502:physiology*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D009559:Nippostrongylus; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011422:Propionates / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018077:Receptors, Leukotriene; D012016:Reference Values; D012039:Regional Blood Flow; D012697:Serine Endopeptidases / Q000097:blood; D013270:Stomach / Q000098:blood supply; D017206:Strongylida Infections / Q000473:pathology* / Q000503:physiopathology*; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D010972:Platelet Activating Factor; D011422:Propionates; D011804:Quinolines; D018077:Receptors, Leukotriene; D014230:Triazoles; C083173:leukotriene C4 receptor; C052518:WEB 2086; C059141:verlukast; D003907:Dexamethasone; D012697:Serine Endopeptidases; D053818:Chymases