Neutrophils, endothelial cells, and cysteinyl leukotrienes: a new approach to neutrophil-dependent inflammation?

Abstract

Cysteinyl leukotrienes (cys-LT) have been historically involved with the pathogenesis of asthma, and cys-LT receptor antagonists and synthesis inhibitors are currently in use for the therapy of this disease. Nevertheless cys-LT possess very potent proinflammatory activities and may play a significant role in inflammatory processes other than asthma. Recent evidences obtained in our laboratory, as well as in others, show that unexpected, biologically significant amounts of cys-LT are formed upon cell-cell cooperation between neutrophils and endothelial cells, resulting from transfer of the synthesis intermediate leukotriene A4 from neutrophils to endothelial cells. Cys-LT formed upon neutrophil adhesion to endothelial cells may contribute to the alterations of microvasculature associated with the inflammatory response. In particular, nonsteroidal anti-inflammatory drug (NSAIDs)-induced neutrophil adhesion to gastric wall microvessels may contribute to the gastric damage associated to the use of NSAIDs. In agreement with this hypothesis, dual 5-LOX/COX inhibitors are characterized by reduced gastric damage when compared to nonspecific COX-inhibitors. Evidence provide support for the involvement of cys-LT in neutrophil-dependent inflammatory responses and suggest new potential application of 5-LO inhibition in anti-inflammatory pharmacological treatment.