Inhibition by HAJ11 of respiratory burst in neutrophils and the involvement of protein tyrosine phosphorylation and phospholipase D activation

Inhibition by HAJ11 of respiratory burst in neutrophils and the involvement of protein tyrosine phosphorylation and phospholipase D activation
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HAJ11 对中性粒细胞呼吸爆发的抑制以及蛋白酪氨酸磷酸化和磷脂酶 D 激活的参与

DOI:
10.1038/sj.bjp.0700861
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发表时间:
1997
影响因子:
7.3
通讯作者:
S. Kuo
S. Kuo
中科院分区:
医学2区
文献类型:
--
作者:
Jih P. Wang;L. Tsao;S. Raung;M. Hsu;S. Kuo

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The possible mechanisms of the inhibitory effect of ethyl 2‐(3‐hydroxyanilino)‐4‐oxo‐4,5‐dihydrofuran‐3‐carboxylate (HAJ11) on the respiratory burst of rat neutrophils in vitro was investigated. HAJ11 caused a reversible and a concentration‐dependent inhibition of formyl‐Met‐Leu‐Phe (fMLP)‐induced superoxide anion (O2−) generation (IC50 4.9±0.7 μm) and O2 consumption (IC50 4.9±1.5 μm). Concanavalin A (Con A)‐ and NaF‐induced O2− generation were also suppressed by HAJ11. However, HAJ11 was a weak inhibitor of the phorbol 12‐myristate 13‐acetate (PMA)‐induced responses. HAJ11 did not scavenge the O2− generation in the xanthine‐xanthine oxidase system and dihydroxyfumaric acid (DHF) autoxidation. HAJ11 showed no activity on fMLP‐induced inositol phosphates formation and [Ca2+]i elevation in intact neutrophils. In addition, HAJ11 had no effect on neutrophil cytosolic phospholipase C (PLC) activity. HAJ11 reduced fMLP‐induced phosphatidic acid (PA) (IC50 29.1±6.5 μm) and phosphatidylethanol (PEt) (IC50 22.6±1.9 μm) formation in a concentration‐dependent manner. HAJ11 also reduced protein tyrosine phosphorylation in neutrophils stimulated by fMLP. HAJ11 was a weak inhibitor of neutrophil cytosolic protein kinase C (PKC) activity, and had a negligible effect on brain PKC. Cellular cyclic nucleotides levels were not altered by HAJ11. In addition, HAJ11 did not affect protein kinase A (PKA) activity. HAJ11 had no effect on the O2− generation of PMA‐activated and arachidonic acid (AA)‐activated NADPH oxidase preparations. Taken together these results indicate that the inhibition of respiratory burst by HAJ11 probably mainly occurs through inhibition of protein tyrosine phosphorylation and phospholipase D (PLD) activity.
DOI: --
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期刊: Journal of immunology (Baltimore, Md. : 1950)
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