Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-γ

作     者：Boneberg, EM Hareng, L Gantner, F Wendel, A Hartung, T 

作者机构：Univ Konstanz D-78457 Constance Germany Byk Gulden Pharmaceut Constance Germany 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第95卷第1期

页      面：270-276页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：双盲法 非格司亭/药理学 基因表达调控/药物作用 基因表达调控/免疫学 干扰素Ⅱ型/生物合成 干扰素Ⅱ型/血液 白细胞计数/药物作用 脂多糖类/药理学 单核细胞/药物作用 单核细胞/免疫学 单核细胞激活素/生物合成 单核细胞激活素/血液 中性白细胞/药物作用 中性白细胞/免疫学 安慰剂 受体 粒细胞集落刺激因子/遗传学 参考值 逆转录聚合酶链反应 成年人 人类 男(雄)性 

摘      要：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.