Prostaglandins and Mucosal Defensive Mechanisms

The first line of mucosa! defence includes the juxtamucosalunstirred layer/pH gradient and the apical surface of the luminal epithelial cells.Many damaging agents, including nonsteroidal anti-inflammatory drugs(NSAIDs), can overwhelm these defences and destroy extensive regions of theluminal epithelium. This damage is readily tolerated in the normal mucosa.Furthermore, a combination of increased mucosal bloodflow, epithelial migration,mucus release, and efflux of bicarbonate- rich fluid usually allows rapidrecovery of mucosa I integrity. In the presence of vascular damage and congestion,however, luminal acid can kill mucosal cells and destroy the substrate necessaryfor repair (by epithelial migration). Damage of this type results in the productionof hemorrhagic erosions, which may then develop into chronic ulceroinflammatorydisease if healing is prevented by excess luminal acid or by impairedmucosal immune response. Endogenous and exogenous prostaglandins couldaffect all aspects of the mucosal defensive responses, from the juxtamucosalunstirred layer/pH gradient (via effects on secretion of bicarbonate, acid andmucus, as well as stimulation of fluid efflux) to the function of the mucosalimmune system. Protection against the acute damage produced by topicallyadministered NSAIDs or concentrated ethanol can result from either administrationof prostaglandins or topical application of'mild irritants'. This is referred toas 'adaptive cytoprotection'. Parenterally administered NSAIDs can also producemucosa! erosions. Protection against this type of damage may depend on theeffects of prostaglandins on neural and contractile elements in the mucosa.Studies on animal models also suggest that by preventing acute hemorrhagicerosions, prostaglandins may prevent the development of chronic ulcer in susceptibleindividuals