Effects of recombinant human granulocyte and macrophage colony-stimulating factors on signal transduction pathways in human granulocytes.
Effects of recombinant human granulocyte and macrophage colony-stimulating factors on signal transduction pathways in human granulocytes.
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DOI：
10.4049/jimmunol.139.10.3422
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发表时间：
1987-11
影响因子：
4.4
通讯作者：
R. Sullivan;J. Griffin;E. Simons;A. Schafer;T. Meshulam;J. Fredette;A. K. Maas;A. Gadenne;J. L. Leavitt;D. Melnick
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文献类型：
--
作者：
R. Sullivan;J. Griffin;E. Simons;A. Schafer;T. Meshulam;J. Fredette;A. K. Maas;A. Gadenne;J. L. Leavitt;D. Melnick
我们研究了重组人活性造血生长因子粒细胞巨噬细胞集落刺激因子（GM-CSFrh）和粒细胞集落刺激因子（G-CSFrh）激活受体介导的转导途径的能力，这些途径与刺激粒细胞的细胞毒功能有关。通过使用一组荧光探针，我们发现这两种生长因子对静息跨膜电位、游离钙离子的细胞内浓度或分离的成熟粒细胞的胞质 pH 值没有产生可检测到的直接影响。然而，当粒细胞通过与GM-CSFrh或G-CSFrh预孵育90分钟来“引发”时，由10(-7)M N-甲酰基-甲硫氨酰-亮氨酰-苯丙氨酸诱导的膜去极化速率大大加快，但游离钙离子的上升速率并未大大加快。在研究解释这些生长因子引发效应的潜在机制时，我们发现虽然它们不会诱导蛋白激酶 C 易位或刺激显着的脱颗粒，但它们各自直接导致花生四烯酸从质膜磷脂中迅速释放。我们的数据表明，虽然 GM-CSFrh 和 G-CSFrh 不激活与粒细胞中受体介导的细胞毒功能激活最明显相关的转导信号，即与膜去极化或细胞内钙离子释放相关的信号，但它们似乎直接诱导酯化至膜磷脂的花生四烯酸的释放，这一事件可能代表受体介导的膜磷脂酶的激活，并且可能有助于“启动”细胞以增强其功能反应性。
We studied the ability of the recombinant human-active hemopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSFrh) and granulocyte colony-stimulating factor (G-CSFrh) to activate receptor-mediated transduction pathways which have been implicated in the stimulation of cytotoxic functions in granulocytes. With the use of a panel of fluorescent probes, we found that these two growth factors exerted no detectable immediate effect on the resting transmembrane electrical potential, the intracellular concentration of free calcium ions, or the cytosolic pH of isolated, mature granulocytes. However, when granulocytes were "primed" by preincubation for 90 min with GM-CSFrh or G-CSFrh, the rate of membrane depolarization induced by 10(-7) M N-formyl-methionyl-leucyl-phenylalanine, but not the rate of rise in free calcium ions, was greatly accelerated. In examining potential mechanisms to account for the priming effect of these growth factors, we found that although they did not induce translocation of protein kinase C or stimulate significant degranulation, they each directly caused prompt release of arachidonic acid from plasma membrane phospholipids. Our data indicate that although GM-CSFrh and G-CSFrh do not activate the transduction signals that have most clearly been implicated in receptor-mediated activation of cytotoxic functions in granulocytes--namely, those coupled to membrane depolarization or release of intracellular calcium ions--they appear directly to induce the release of arachidonic acid esterified to membrane phospholipids, an event which may represent the receptor-mediated activation of membrane phospholipases and which may contribute to the "priming" of the cells for enhancement of their functional responsiveness.