Granulocyte-macrophage colony-stimulating factor and human neutrophils: role of guanine nucleotide regulatory proteins.

Granulocyte-macrophage colony-stimulating factor and human neutrophils: role of guanine nucleotide regulatory proteins.
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DOI:
10.1073/pnas.86.10.3569
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发表时间:
1989-05
影响因子:
11.1
通讯作者:
J. Gomez-Cambronero;M. Yamazaki;F. Metwally;T. Molski;V. Bonak;C. Huang;E. Becker;R. Sha’afi
J. Gomez-Cambronero;M. Yamazaki;F. Metwally;T. Molski;V. Bonak;C. Huang;E. Becker;R. Sha’afi
中科院分区:
综合性期刊1区
文献类型:
--
作者:
J. Gomez-Cambronero;M. Yamazaki;F. Metwally;T. Molski;V. Bonak;C. Huang;E. Becker;R. Sha’afi

文献摘要

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添加粒细胞-巨噬细胞集落刺激因子(GM-CSF)的人中性粒细胞引起的基础和fMet-Leu-Phe刺激的Na+内流和细胞内pH值的增加的快速增加。增加可以看到早在5分钟后添加GM-CSF。由GM-CSF产生的变化被阿米洛利完全抑制,并且在百日咳毒素处理的细胞中显著降低。GM-CSF对Na+/H+交换机制的刺激抑制了fMet-Leu-Phe或佛波醇12-肉豆蔻酸酯13-乙酸酯对该系统的进一步刺激。此外,从GM-CSF处理的中性粒细胞分离的膜制剂具有较高的基础和刺激的GT3活性。在百日咳毒素处理的细胞中,基础和fMet-Leu-Phe-或血小板活化因子刺激的GTdR活性降低。用GM-CSF预处理的细胞比对照细胞积累更多的放射性磷酸盐,并且这种增加被百日咳毒素处理减弱。此外,GM-CSF导致分子量为118 kDa、92 kDa、78 kDa、54 kDa和40 kDa的五种蛋白质的酪氨酸磷酸化水平快速增加。这些结果清楚地表明,GM-CSF本身可以启动几种变化,这些变化部分是由百日咳毒素敏感的鸟嘌呤核苷酸调节蛋白介导的。
The addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to human neutrophils causes a rapid increase in the basal and fMet-Leu-Phe-stimulated Na+ influx and an increase in intracellular pH. The increase can be seen as early as 5 min after the addition of GM-CSF. Changes produced by GM-CSF are totally inhibited by amiloride and are significantly reduced in pertussis toxin-treated cells. The stimulation of the Na+/H+ exchange mechanism by GM-CSF inhibits further stimulation of this system with either fMet-Leu-Phe or phorbol 12-myristate 13-acetate. In addition, membrane preparations isolated from GM-CSF-treated neutrophils have higher basal and stimulated GTPase activities. The basal and the fMet-Leu-Phe- or platelet-activating factor-stimulated GTPase activities are reduced in pertussis toxin-treated cells. Cells pretreated with GM-CSF accumulate more radioactive phosphate than control cells, and this increase is diminished by pertussis toxin treatment. In addition, GM-CSF causes a rapid increase in the tyrosine phosphorylation levels of five proteins with molecular masses of 118 kDa, 92 kDa, 78 kDa, 54 kDa, and 40 kDa. These results clearly show that GM-CSF, on its own, can initiate several changes and that these changes are mediated in part by the pertussis toxin-sensitive guanine nucleotide regulatory protein.