Gastric ulceration: critical events at the neutrophil–endothelium interface

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Abstract
Neutrophil adherence to the vascular endothelium and the subsequent release of oxygen-derived free radicals and proteolytic enzymes has been implicated as a critical event in the pathogenesis of various forms of gastrointestinal ulceration. This paper reviews the evidence that events at the neutrophil-endothelium interface are important in the pathogenesis of gastric ulceration induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Endothelial injury occurs within minutes of NSAID administration and appears to be attributable to neutrophil adherence and activation. Neutrophil adherence in response to NSAIDs may occur as a consequence of inhibition of endothelial prostaglandin synthesis, but it appears to involve a lipoxygenase product, such as leukotriene B4. Prevention of neutrophil adherence to the vascular endothelium results in near-complete prevention of experimental NSAID gastropathy. Depletion of circulating neutrophils also results in reduced susceptibility to NSAID-induced mucosal injury. As prostaglandins are potent inhibitors of neutrophil adherence and activation, it is possible that the neutrophil–endothelium interface represents one of the most important targets of action of these compounds in terms of their ability to prevent or reduce the severity of NSAID-induced ulceration.Key words: ulcer, mucosal blood flow, prostaglandin, neutrophil, leukotriene.

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