In vivo treatment with granulocyte colony-stimulating factor results in divergent effects on neutrophil functions measured in vitro

In vivo treatment with granulocyte colony-stimulating factor results in divergent effects on neutrophil functions measured in vitro
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DOI:
10.1182/blood.v92.11.4366.423k23_4366_4374
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发表时间:
1998-12-01
期刊:
影响因子:
20.3
通讯作者:
Ambruso, DR
Ambruso, DR
中科院分区:
医学1区
文献类型:
--
作者:
Leavey, PJ;Sellins, KS;Ambruso, DR

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我们已经研究了粒细胞集落刺激因子(G-CSF)给药对正常人的各种功能和生化中性粒细胞特性,涉及到主机防御的影响。G-CSF对中性粒细胞(多形核白细胞[PMN])的趋化性有不良影响。虽然这可以部分解释为减少组装中性粒细胞F-肌动蛋白,我们也认识到一个升高的胞浆钙动员和中性粒细胞CD 11b的正常上调。G-CSF导致中性粒细胞对金黄色葡萄球菌的杀伤率降低,细菌:中性粒细胞比例为10:1,正常杀伤率为1:1。与此相关,我们证明了不同的影响呼吸爆发的完整细胞和不同的影响中性粒细胞颗粒的标记蛋白质的含量。虽然G-CSF可能导致细胞膜中细胞色素B(558)的含量增加,但它不会改变胞浆氧化酶组分的含量。治疗后,嗜天青颗粒标记物髓过氧化物酶含量正常,特异性颗粒标记物乳铁蛋白含量下降,溶菌酶含量正常(在两种颗粒类别中均发现)。最后,G-CSF治疗显著降低了中性粒细胞的凋亡率。因此,考虑到不同的功能和生化活性,G-CSF治疗的真实的益处可能在于增加中性粒细胞的数量和存活。(C)1998年,美国血液学会。
We have studied the effects of granulocyte colony-stimulating factor (G-CSF) administration to normal individuals on a variety of functional and biochemical neutrophil characteristics that relate to host defense. G-CSF adversely affected neutrophil (polymorphonuclear leukocyte [PMN]) chemotaxis. While this could be partially explained by reduced assembly of neutrophil F-actin, we also recognized an elevated cytosolic calcium mobilization and a normal upregulation of neutrophil CD11b. G-CSF resulted in reduced PMN killing of Staphylococcus aureus with a 10:1 (bacteria: neutrophil) ratio and normal killing with a 1:1 ratio. In association with this, we demonstrated divergent effects on the respiratory burst of intact cells and divergent effects on the content of marker proteins for neutrophil granules. While G-CSF may have resulted in increased content of cytochrome b(558) in the cell membrane, it did not alter the amounts of cytosolic oxidase components. After therapy, there was normal content of the azurophilic granule marker, myeloperoxidase, decreased content of the specific granule marker, lactoferrin, and normal content of lysozyme (found in both granules classes). Finally, G-CSF therapy markedly reduced the apoptotic rate of the isolated neutrophil. Therefore, considering disparate functional and biochemical activities, the real benefit of G-CSF therapy may lie in enhanced number and survival of neutrophils. (C) 1998 by The American Society of Hematology.