Inhibition of fMLP-triggered respiratory burst of human monocytes by adenosine:: involvement of A3 adenosine receptor

被引:43
作者
Broussas, M
Cornillet-Lefèbvre, P
Potron, G
Nguyen, P
机构
[1] CHU Robert Debre, Cent Hematol Lab, F-51092 Reims, France
[2] CHU Robert Debre, UPRES EA2070, Lab Immunol & Hematol, IFR Biomol 53, F-51092 Reims, France
关键词
NADPH oxidase; chemiluminescence; transduction pathway;
D O I
10.1002/jlb.66.3.495
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Adenosine (Ado) is a potent anti-inflammatory agent acting oil a variety of cell functions, However, its effects on human monocytes have been less well characterized. We investigated the effect of Ado and its receptor-specific analogs on NADPH oxidase activity with the use of luminol-enhanced chemiluminescence (CL), Adenosine inhibited fMLP-triggered NADPH oxidase activity with a maximal inhibition of 55 +/- 5%. IB-MECA, a selective A3 Ado receptor agonist reduced fMLP triggered NADPH oxidase activity more potently than the A2 receptor agonist CGS 2180 HCl (CGS) and the A1 Ado receptor agonist N-2-phenylethyl-adenosine (R-PIA), The inhibitory effect of Ado was reversed by neither the A1 Ado receptor antagonist 1,3-dipropyl-8(2-amino-4chlorophenyl)-xanthine (PACPX) nor the A2 Ado receptor antagonist 3,7-dimethyl-1-(2-propynyl)xanthine (DMPX), It was significantly reversed by the A1/A3 Ado receptor antagonist xanthine amine congener (XAC). Pretreatment of monocytes by cytochalasin B reversed the effect of Ado but not of dibutyryl cAMP (dBcAMP) on fMLP-CL response. BT 5720, a specific cAMP-dependent protein kinase inhibitor completely counteracted the inhibition of NADPH oxidase activity by dBcAMP but not by Ado, Using flow cytometry, we observed that Ado did not inhibit intracellular oxidative metabolism, whereas dBcAMP did, Furthermore, the inhibition of NADPH oxidase activity by Ado was not mediated by changes in cytosolic calcium, These results demonstrated that Ado inhibited NADPH oxidase activity via A3 Ado receptor independently of cAMP elevation or changes in calcium mobilization.
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页码:495 / 501
页数:7
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