Biosynthetic human GM-CSF modulates the number and affinity of neutrophil f-Met-Leu-Phe receptors.

Biosynthetic human GM-CSF modulates the number and affinity of neutrophil f-Met-Leu-Phe receptors.
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DOI:
10.4049/jimmunol.137.11.3584
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发表时间:
1986-12
影响因子:
4.4
通讯作者:
R. Weisbart;D. Golde;J. Gasson
R. Weisbart;D. Golde;J. Gasson
中科院分区:
医学2区
文献类型:
--
作者:
R. Weisbart;D. Golde;J. Gasson

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人粒细胞-巨噬细胞集落刺激因子(GM-CSF)通过激活N-甲酰-甲硫基-亮氨酰-苯丙氨酸(f-Met-Leu-Phe)增强中性粒细胞的趋化和氧化代谢来调节成熟中性粒细胞的功能。我们的研究建立了f-Met-Leu-Phe受体数量和亲和力与中性粒细胞趋化和氧化代谢之间的关系。短暂(5-15分钟)暴露于生理浓度的GM-CSF(10 PM至100 PM)可将f-Met-Leu-Phe诱导的中性粒细胞趋化能力提高85%,与高亲和力中性粒细胞f-Met-Leu-Phe受体的快速三倍增加(46,000个/细胞至150,000个/细胞)相关。中性粒细胞与GM-CSF孵育时间延长(1至2小时),伴随着低亲和力f-Met-Leu-Phe受体的变化(Kd=29 nM至Kd=99 nM),并伴随着增强中性粒细胞氧化代谢的启动。此外,在中性粒细胞与GM-CSF孵育更长时间后,对f-Met-Leu-Phe的趋化反应增强不再明显。这些结果表明,单个淋巴因子(GM-CSF)诱导中性粒细胞f-Met-Leu-Phe受体数目和亲和力的顺序变化可能增强不同的生理反应。
Human granulocyte-macrophage colony-stimulating factor (GM-CSF) modulates the function of mature neutrophils by priming for enhanced chemotaxis and oxidative metabolism in response to N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe). Our studies establish a relationship between f-Met-Leu-Phe receptor number and affinity and neutrophil chemotaxis and oxidative metabolism. A brief (5- to 15-min) exposure to physiologic concentrations of GM-CSF (10 pM to 100 pM) enhances f-Met-Leu-Phe-induced neutrophil chemotaxis by 85%, correlating with a rapid threefold increase (46,000/cell to 150,000/cell) in high-affinity neutrophil f-Met-Leu-Phe receptors. More prolonged incubation (1 to 2 hr) of neutrophils with GM-CSF is accompanied by a change to low-affinity f-Met-Leu-Phe receptors (Kd = 29 nM to Kd = 99 nM) concomitant with priming for enhanced neutrophil oxidative metabolism. Moreover, enhanced chemotactic responses to f-Met-Leu-Phe are no longer evident after more prolonged incubation of neutrophils with GM-CSF. These results show that a single lymphokine (GM-CSF) induces sequential changes in neutrophil f-Met-Leu-Phe receptor number and affinity that may enhance different physiologic responses.