Temporal adaptation of neutrophil oxidative responsiveness to n-formyl-methionyl-leucyl-phenylalanine. Acceleration by granulocyte-macrophage colony stimulating factor.
Temporal adaptation of neutrophil oxidative responsiveness to n-formyl-methionyl-leucyl-phenylalanine. Acceleration by granulocyte-macrophage colony stimulating factor.
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DOI：
10.4049/jimmunol.141.7.2400
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发表时间：
1988-10
影响因子：
4.4
通讯作者：
D. English;H. Broxmeyer;T. Gabig;L. Akard;D. Williams;R. Hoffman
中科院分区：
文献类型：
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作者：
D. English;H. Broxmeyer;T. Gabig;L. Akard;D. Williams;R. Hoffman
本研究旨在阐明纯化的重组人粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 增强趋化肽 FMLP 引发的中性粒细胞氧化反应的机制。先前的研究表明，GM-CSF 引发中性粒细胞对 FMLP 反应的诱导相对较慢，需要在体外孵育 90 至 120 分钟，与细胞质游离 Ca2+ 水平增加无关，但与细胞表面 FMLP 受体的上调有关。我们已经证实了这些发现并进一步描述了 GM-CSF 启动过程。我们发现，GM-CSF 对中性粒细胞氧化反应性的影响是以温度依赖性方式诱导的，并且在用 FMLP 刺激之前充分洗涤细胞以去除生长因子时，这种影响不会逆转。 GM-CSF 的功能增强不需要细胞外 Ca2+，并且在体外培养期间单独使用 GM-CSF 不会对中性粒细胞的 32P 标记磷脂含量造成可检测到的变化。我们的数据表明，GM-CSF 通过加速自发发生的过程对中性粒细胞产生影响，并导致细胞表面 FMLP 受体和 FMLP 氧化反应上调。因此，结果表明，就氧化激活而言，循环终末期多形核白细胞对 FMLP 无反应或反应低下；随着细胞离开循环后表面 FMLP 受体逐渐部署，功能反应性急剧增加。因此，随着中性粒细胞的成熟，它们对 FMLP 的反应会发生变化，这对于有效的宿主防御可能至关重要。在 37 摄氏度时，GM-CSF 显着增强了这一过程。我们得出的结论是，全身释放或在感染和炎症部位释放的内源性 GM-CSF 通过加速响应多形核白细胞的功能成熟，可能在宿主防御中发挥重要作用。
This investigation was undertaken to clarify the mechanism by which purified recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) potentiates neutrophil oxidative responses triggered by the chemotactic peptide, FMLP. Previous studies have shown that GM-CSF priming of neutrophil responses to FMLP is induced relatively slowly, requiring 90 to 120 min of incubation in vitro, is not associated with increased levels of cytoplasmic free Ca2+, but is associated with up-regulation of cell-surface FMLP receptors. We have confirmed these findings and further characterized the process of GM-CSF priming. We found that the effect of GM-CSF on neutrophil oxidative responsiveness was induced in a temperature-dependent manner and was not reversed when the cells were washed extensively to remove the growth factor before stimulation with FMLP. Extracellular Ca2+ was not required for functional enhancement by GM-CSF and GM-CSF alone effected no detectable alteration in the 32P-labeled phospholipid content of neutrophils during incubation in vitro. Our data indicate that GM-CSF exerts its influence on neutrophils by accelerating a process that occurs spontaneously and results in up-regulation of both cell-surface FMLP receptors and oxidative responsiveness to FMLP. Thus, the results demonstrate that, with respect to oxidative activation, circulating endstage polymorphonuclear leukocytes are nonresponsive or hyporesponsive to FMLP; functional responsiveness increases dramatically as surface FMLP receptors are gradually deployed after the cells leave the circulation. Thus, as neutrophils mature, their responsiveness to FMLP changes in a manner which may be crucial for efficient host defense. At 37 degrees C, this process is markedly potentiated by GM-CSF. We conclude that endogenous GM-CSF, released systemically or at sites of infection and inflammation, potentially plays an important role in host defense by accelerating functional maturation of responding polymorphonuclear leukocytes.