Neutrophil migration in inflammation: nitric oxide inhibits rolling, adhesion and induces apoptosis

被引:123
作者
Dal Secco, D
Paron, JA
de Oliveira, SHP
Ferreira, H
Silva, JS
Cunha, FDQ
机构
[1] Univ Sao Paulo, Sch Med, Dept Pharmacol, BR-14049900 Ribeirao Preto, SP, Brazil
[2] Univ Sao Paulo, Sch Med, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, Brazil
[3] Aracatuba State Univ, Sch Dent, Dept Basic Sci, Sao Paulo, Brazil
来源
NITRIC OXIDE-BIOLOGY AND CHEMISTRY | 2003年 / 9卷 / 03期
基金
巴西圣保罗研究基金会;
关键词
nitric oxide; nitric oxide synthase; inflammation; apoptosis; adhesion; neutrophil migration;
D O I
10.1016/j.niox.2003.11.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
There is controversy in the literature over whether nitric oxide (NO) released during the inflammatory process has a pro- or inhibitory effect on neutrophil migration. The aim of the present investigation was to clarify this situation. Treatment of rats with non-selective, N-G-nitro-L-arginine (nitro), or selective inducible NO synthase (iNOS), aminoguanidine (amino) inhibitors enhanced neutrophil migration 6h after the administration of low, but not high, doses of carrageenan (Cg) or Escherichia coli endotoxin (LPS). The neutrophil migration induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was also enhanced by nitro or amino treatments. The enhancement of Cg-induced neutrophil migration by NOS inhibitor treatments was reversed by co-treatment with L-arginine, suggesting an involvement of the L-arginine/NOS pathway in the process. The administration of Cg in NOS deficient (iNOS(-/-)) mice also enhanced the neutrophil migration compared with wild type mice. This enhancement was markedly potentiated by treatment of iNOS(-/-) mice with nitro. Investigating the mechanisms by which NOS inhibitors enhanced the neutrophil migration, it was observed that they promoted an increase in Cg-induced rolling and adhesion of leukocytes to endothelium and blocked the apoptosis of emigrated neutrophils. Similar results were observed in iNOS-/- mice, in which these mechanisms were potentiated and reverted by nitro and L-arginine treatments, respectively. In conclusion, these results suggest that during inflammation, NO released by either constitutive NOS (cNOS) or iNOS down-modulates the neutrophil migration. This NO effect seems to be a consequence of decreased rolling and adhesion of the neutrophils on endothelium and also the induction of apoptosis in migrated neutrophils. (C) 2003 Elsevier Inc. All rights reserved.
引用
收藏
页码:153 / 164
页数:12
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