Neutrophils, Endothelial Cells, and Cysteinyl Leukotrienes: A New Approach to Neutrophil-Dependent Inflammation?

• Published in: Biochemical and biophysical research communications Vol. 283; no. 5; pp. 1003 - 1006
• Main Authors: Sala, Angelo, Folco, Giancarlo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 25.05.2001
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - toxicity; Asthma - physiopathology; Cysteine - physiology; Edema; Endothelium, Vascular - physiology; Endothelium, Vascular - physiopathology; Gastric Mucosa - drug effects; Gastric Mucosa - pathology; Humans; Inflammation - physiopathology; Inflammation Mediators - physiology; Intestinal Mucosa - drug effects; Intestinal Mucosa - pathology; Leukotrienes - physiology; Muscle, Smooth, Vascular - physiology; Muscle, Smooth, Vascular - physiopathology; Neutrophils - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.4865

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.