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一氧化氮合酶抑制剂在体外减弱人单核细胞趋化性。

Nitric oxide synthase inhibitors attenuate human monocyte chemotaxis in vitro.

作者信息

Belenky S N, Robbins R A, Rubinstein I

机构信息

Research Service, Department of Veterans Affairs Medical Center, Omaha, Nebraska.

出版信息

J Leukoc Biol. 1993 May;53(5):498-503. doi: 10.1002/jlb.53.5.498.

DOI:10.1002/jlb.53.5.498
PMID:7684763
Abstract

Nitric oxide synthase (NOS) inhibitors have been shown to modulate neutrophil migration. We hypothesized that the NOS inhibitors NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and L-canavanine (L-CAN) also modulate human peripheral blood monocyte chemotaxis. To test this hypothesis, monocyte chemotaxis toward formylmethionylleucyl-phenylalanine (fMLP) was assessed using a modified blindwell chemotaxis chamber technique. L-NMMA and L-NAME, but not D-NMMA or L-CAN, significantly attenuated fMLP-induced monocyte chemotaxis (P < .05). L-Arginine and sodium nitroprusside, but not D-arginine, reversed NOS inhibitor-induced responses. Dibutryl cyclic guanyl monophosphate (cGMP) attenuated the inhibitory effects of L-NMMA on monocyte chemotaxis (P < .05). Finally, fMLP increased cGMP generation by monocytes, which was significantly attenuated by L-NMMA (P < .05). These data indicate that the L-arginine/NO biosynthetic pathway regulates human monocyte chemotaxis in vitro.

摘要

一氧化氮合酶(NOS)抑制剂已被证明可调节中性粒细胞的迁移。我们推测,NOS抑制剂N-甲基-L-精氨酸(L-NMMA)、N-硝基-L-精氨酸甲酯(L-NAME)和刀豆氨酸(L-CAN)也可调节人外周血单核细胞的趋化作用。为了验证这一假设,我们使用改良的盲孔趋化室技术评估了单核细胞对甲酰甲硫氨酰亮氨酰苯丙氨酸(fMLP)的趋化作用。L-NMMA和L-NAME可显著减弱fMLP诱导的单核细胞趋化作用(P <.05),而D-NMMA或L-CAN则无此作用。L-精氨酸和硝普钠可逆转NOS抑制剂诱导的反应,而D-精氨酸则不能。二丁酰环磷酸鸟苷(cGMP)可减弱L-NMMA对单核细胞趋化作用的抑制效果(P <.05)。最后,fMLP可增加单核细胞产生的cGMP,而L-NMMA可显著减弱这种增加(P <.05)。这些数据表明,L-精氨酸/一氧化氮生物合成途径在体外调节人单核细胞的趋化作用。

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