Nitric oxide-releasing compounds inhibit neutrophil adhesion to endothelial cells

被引:59
|
作者
Kosonen, O
Kankaanranta, H
Malo-Ranta, U
Moilanen, E
机构
[1] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland
[2] Tampere Univ Hosp, Dept Resp Med, Tampere 33521, Finland
[3] Tampere Univ Hosp, Dept Clin Chem, Tampere 33521, Finland
基金
芬兰科学院;
关键词
nitric oxide (NO); nitric oxide (NO)-releasing compound; adhesion; CD11/CD18;
D O I
10.1016/S0014-2999(99)00581-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In the present work, we demonstrated that chemically different nitric oxide (NO)-releasing compounds inhibit tumor necrosis factor alpha (TNF-alpha)-induced polymorphonuclear leukocyte adhesion to endothelial cells in vitro. Two mesoionic oxatriazole derivatives GEA 3162 (1,2,3,4-oxatriazolium,5-amino-3(3,4-dichlorophenyl)-chloride) and GEA 3175 (1,2,3,4-oxatriazolium,-3-(3-chloro-2-methylphenyl)-5-[[(4-methylphenyl)sulfonyl]amino]-, hydroxide inner salt) were compared to the earlier-known NO donor SIN-1 (3-morpholino-sydnonimine). GEA 3162 (3-10 mu M) and GEA 3175 (10-30 mu M) inhibited human polymorphonuclear leukocyte adhesion to B-4 endothelial cells in a dose-dependent manner being more potent than SIN-1. In the present model, leukocytes rather than endothelial cells seemed to be the target of the effect of NO. Flow cytometric analysis showed that NO-releasing compounds did not alter TNF-alpha induced CD11/CD18 surface expression in polymorphonuclear leukocytes. The inhibitory action of NO-releasing compounds on adhesion paralleled with the increased synthesis of cGMP in polymorphonuclear leukocytes. Analogues of cGMP inhibited polymorphonuclear leukocyte adhesion indicating a role for cGMP in the action of NO donors. The results suggest that exogenous NO in the form of NO-releasing compounds inhibits polymorphonuclear leukocyte adhesion to endothelial cells, which may be implicated in the regulation of leukocyte migration and leukocyte-mediated tissue injury. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:111 / 117
页数:7
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