Neutrophils, endothelial cells, and cysteinyl leukotrienes: a new approach to neutrophil-dependent inflammation?
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.
Sala
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Department of Pharmacological Sciences, Università degli Studi di Milano, Via Balzaretti 9, Milan, 20133, Italy. angelo.sala@unimi.it
Folco
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D001249:Asthma / Q000503:physiopathology; D003545:Cysteine / Q000502:physiology*; D004487:Edema; D004730:Endothelium, Vascular / Q000502:physiology* / Q000503:physiopathology; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D015289:Leukotrienes / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D003545:Cysteine