MAST-CELLS DO NOT CONTRIBUTE TO NONSTEROIDAL ANTIINFLAMMATORY DRUG-INDUCED GASTRIC-MUCOSAL INJURY IN RODENTS

Background: By releasing pro-ulcerogenic mediators, mast cells may con tribute to the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). Methods: To study this, rat and mous e models of NSAID-induced gastric damage were used in which administra tion of indomethacin causes haemorrhagic injury in the corpus region o f the stomach, and the ''re-feeding'' model in which penetrating antra l ulcers are induced in the rat by naproxen, Mast cell degranulation w as determined histologically and by measurement of tissue and serum le vels of rat mast cell protease-II, a mediator specific to mucosal mast cells, The effects of either increasing or decreasing the number of g astric mucosal mast cells on the susceptibility of the stomach to inju ry induced by indomethacin were also studied. Results: Gastric injury induced by indomethacin was not accompanied by significant mast cell d egranulation. Moreover, neither increasing nor decreasing the number o f gastric mucosal mast cells had a significant effect on the susceptib ility of the gastric mucosa to damage induced by indomethacin, In the re-feeding model, prior depletion of gastric mucosal mast cells did no t significantly affect the severity of antral ulceration induced by na proxen, nor the ability of prostaglandin E(2) to prevent this damage, Finally, indomethacin-induced damage was similar in severity in mice w ith a genetic defect resulting in the complete absence of mast cells a s it was in normal, congenic littermates. Conclusion: Mast cells do no t play a significant role in the development of gastric injury induced by acute NSAID administration in the rat or mouse.