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 ac tivation on mucosal resistance to injury has not previously been exami ned. In this study, rats were sensitized to the nematode Nippostrongyl us brasiliensis and were studied 35-42 days later. With use of an ex v ivo 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 simila r levels of ethanol-induced gastric injury as control rats, despite ha ving significantly greater numbers of mucosal mast cells. However, ant igen administration, which did not in itself produce mucosal injury, s ignificantly augmented (similar to 3-fold) the extent of injury in sen sitized but not control rats. Prior treatment with dexamethasone deple ted mucosal mast cells in control and sensitized rats. Moreover, this treatment abolished the increase in mucosal injury observed in sensiti zed rats treated with antigen and topical ethanol. Pretreatment with a leukotriene D-4-receptor antagonist, but not a platelet-activating fa ctor-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 mas t cell number per se does not influence mucosal susceptibility to inju ry; however, activation of mast cells markedly increases the susceptib ility to injury through a peptidoleukotriene-dependent mechanism.