NITRIC-OXIDE SYNTHASE INHIBITORS ATTENUATE HUMAN MONOCYTE CHEMOTAXIS INVITRO

NITRIC-OXIDE SYNTHASE INHIBITORS ATTENUATE HUMAN MONOCYTE CHEMOTAXIS INVITRO
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DOI:
10.1002/jlb.53.5.498
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发表时间:
1993-05-01
影响因子:
5.5
通讯作者:
RUBINSTEIN, I
RUBINSTEIN, I
中科院分区:
医学3区
文献类型:
--
作者:
BELENKY, SN;ROBBINS, RA;RUBINSTEIN, I

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一氧化氮合酶(NOS)抑制剂已被证明可以调节中性粒细胞迁移。我们假设NOS抑制剂N(G)-单甲基-L-精氨酸(L-NMMA)、N(G)-硝基-L-精氨酸甲酯(L-NAME)和L-刀豆氨酸(L-CAN)也调节人外周血单核细胞趋化性。为了验证这一假设,单核细胞趋化性对甲酰甲硫氨酰-亮氨酰-苯丙氨酸(fMLP)进行了评估,使用改良的Blindwell趋化室技术。L-NMMA和L-NAME,而不是D-NMMA或L-CAN,显著减弱fMLP诱导的单核细胞趋化性(P <0.05)。L-精氨酸和硝普钠,但不是D-精氨酸,逆转NOS神经元诱导的反应。环磷酸鸟苷(cGMP)可减弱L-NMMA对单核细胞趋化性的抑制作用(P <0.05)。最后,fMLP增加单核细胞产生cGMP,这被L-NMMA显著减弱(P <0.05)。这些数据表明L-精氨酸/NO生物合成途径在体外调节人类单核细胞趋化性。
Nitric oxide synthase (NOS) inhibitors have been shown to modulate neutrophil migration. We hypothesized that the NOS inhibitors N(G)-monomethyl-L-arginine (L-NMMA), N(G)-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 formylmethionyl-leucyl-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.