Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ
Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ
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DOI：
10.1182/blood.v95.1.270
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发表时间：
2000-01-01
期刊：
影响因子：
20.3
通讯作者：
Hartung, T
中科院分区：
文献类型：
--
作者：
Boneberg, EM;Hareng, L;Hartung, T
在一项双盲、安慰剂对照、随机研究中，10名健康男性接受单剂量480 μ g粒细胞集落刺激因子（G-CSF）或生理盐水。用10 μ g/mL内毒素刺激从志愿者采集的血液，并通过酶联免疫吸附测定法测量释放的细胞因子。流式细胞术和逆转录聚合酶链反应检测白细胞G-CSF受体的表达。通过在G-CSF存在下用内毒素挑战分离的白细胞群以释放细胞因子来测试这些受体的功能活性。G-CSF处理减弱了促炎细胞因子肿瘤坏死因子（TNF）-α、白细胞介素（IL）-12、IL-1 β和干扰素（IFN）-γ在离体脂多糖（LPS）刺激的全血中的释放。在来自未处理志愿者的血液中，G-CSF在体外的存在也减弱了LPS刺激的这些细胞因子的释放。G-CSF在体外也减弱了从淘析纯化的单核细胞的TNF-α释放。在10 ng/mL重组TNF-α存在下，G-CSF对LPS诱导的IFN-γ释放的减弱在全血中减弱。然而，G-CSF对用抗CDS或TNF-α和IL-12的组合刺激的分离的淋巴细胞的IFN-γ释放没有这样的作用。通过RT-PCR以及流式细胞术，在人中性粒细胞和单核细胞中检测到G-CSF受体表达，但在淋巴细胞中未检测到。这些结果表明，在单核细胞上表达的G-CSF受体在调节单核因子释放中起作用。我们的结论是，从淋巴细胞释放的IFN-γ的衰减不是G-CSF对这些细胞的直接影响，而是由于G-CSF抑制单核细胞IL-12和TNF-α的释放。(C)2000年，美国血液学会。
In a double-blind, placebo-controlled, randomized study, 10 healthy men received either a single dose of 480 mu g granulocyte colony-stimulating factor (G-CSF) or saline. Blood taken from the volunteers was stimulated with 10 mu g/mL endotoxin and released cytokines were measured by enzyme-linked immunosorbent assay. Expression of G-CSF receptors on leukocytes was examined by flow cytometry and reverse transcriptase-polymerase chain reaction. Functional activity of these receptors was tested by challenging isolated leukocyte populations to release cytokines with endotoxin in the presence of G-CSF. The G-CSF treatment attenuated the release of the proinflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-12, IL-1 beta, and interferon (IFN)-gamma in ex vivo lipopolysaccharide (LPS)-stimulated whole blood, In blood from untreated volunteers the presence of G-CSF in vitro also attenuated the LPS-stimulated release of these cytokines. G-CSF in vitro also attenuated TNF-alpha release from elutriation-purified monocytes, In the presence of 10 ng/mL recombinant TNF-alpha, the attenuation of LPS-inducible lFN-gamma release by G-CSF was blunted in whole blood. However, G-CSF had no such effect on IFN-gamma release from isolated lymphocytes stimulated with anti-CDS or a combination of TNF-alpha and IL-12, G-CSF receptor expression was detected in human neutrophils and monocytes but not in lymphocytes by means of RT-PCR as well as flow cytometry, These results indicate that G-CSF receptors expressed on monocytes are functional in modulating monokine release. We conclude that the attenuation of IFN-gamma release from lymphocytes is not a direct effect of G-CSF on these cells but is rather due to the inhibition of monocytic IL-12 and TNF-alpha release by G-CSF. (C) 2000 by The American Society of Hematology.