Suppression of Leukotriene B4 Biosynthesis by Endogenous Adenosine in Ligand-activated Human Neutrophils

• DOI: 10.1084/jem.186.8.1401
• Publication Date: 2002-07-26T16:49:30Z
• Authors: Eric Krump; Serge Picard; Joseph Mancini; Pierre Borgeat
• Keywords: Leukotriene B4

Adenosine (Ado) has been shown to suppress several functional responses of human polymorphonuclear leukocytes (PMNs). The current study investigated whether endogenous Ado regulates the biosynthesis leukotriene (LT)B4 in ligand-stimulated PMNs. Measurements PMN resuspended Hanks' buffered salt solution (HBSS) or plasma showed a cell concentration– and time–dependent accumulation nucleoside. removal with either deaminase blockade its action by A2a receptor antagonist, 8-(3-chlorostyryl) caffeine, markedly increased LTB4 upon ligand stimulation HBSS. Similarly, synthesis PMNs (containing recombinant LTA4 hydrolase allow conversion protein-bound LTA4) was strongly enhanced addition deaminase. Addition red blood cells suspensions mimicked effect adding enhancing stimulation. This on blocked dipyridamole, an inhibitor transport, captopril, hydrolase. These results demonstrate that efficiently downregulates suspensions, pointing out potentially important regulatory function inflammatory exudates. also unveil dual role for upregulating biosynthesis, namely, released activated