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首页> 外文期刊>Infection and immunity >Enhancement of oxidative response and damage caused by human neutrophils to Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon.
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Enhancement of oxidative response and damage caused by human neutrophils to Aspergillus fumigatus hyphae by granulocyte colony-stimulating factor and gamma interferon.

机译：粒细胞集落刺激因子和γ干扰素增强人嗜中性粒细胞对烟曲霉菌丝的氧化反应和损害。

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摘要

Invasive aspergillosis is a serious fungal infection caused by the proliferation and invasion of Aspergillus hyphae in tissue. Neutrophils (PMNs) are the most important line of defense against Aspergillus hyphae. To investigate the role of granulocyte colony-stimulating factor (G-CSF) and gamma interferon (IFN-gamma) against Aspergillus fumigatus, we studied the effects of the two cytokines on the oxidative burst and the capacity of normal human PMNs to damage hyphae of the organism. G-CSF enhanced PMN oxidative burst measured as superoxide anion (O2-) production in response to N-formylmethionyl leucyl phenylalanine, serum opsonized hyphae, and nonopsonized hyphae by 75, 37, and 24%, respectively, compared with control PMNs (P < 0.015). IFN-gamma also induced increases of 52, 71, and 96%, respectively, in response to the same stimuli (P < 0.006). In addition, the capacity of PMNs to damage hyphae as measured by the 3-4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MMT) colorimetric metabolic assay was significantly enhanced by G-CSF and IFN-gamma (P < 0.01 and < 0.05, respectively). The enhancement was achieved irrespective of serum opsonization of the hyphae, suggesting upregulatory actions of the two cytokines on signal pathways specific for opsonized and nonopsonized hyphae. The combination of the two cytokines exhibited an additive effect at the higher concentrations compared with the effects of the cytokines alone (P < 0.05). Pretreatment of PMNs with protein synthesis inhibitors showed that IFN-gamma activates PMN function through transcriptional regulation, whereas the effect of G-CSF does not require new proteins. These in vitro effects suggest modulatory roles for G-CSF and IFN-gamma in the host defense against Aspergillus hyphae irrespective of serum opsonization and a potential utility of the cytokines as adjuncts for the prevention and possible treatment of invasive aspergillosis.
机译：侵袭性曲霉病是由组织中的曲霉菌丝的增殖和侵袭引起的严重的真菌感染。中性粒细胞（PMN）是抵抗曲霉菌丝的最重要的防御方法。为了研究粒细胞集落刺激因子（G-CSF）和γ干扰素（IFN-γ）对烟曲霉的作用，我们研究了这两种细胞因子对氧化爆发的影响以及正常人PMNs破坏烟丝菌丝的能力。有机体。与N-甲酰基甲硫基亮氨酰苯丙氨酸，血清调理菌丝和非调理菌丝相比，G-CSF增强的PMN氧化爆发（作为超氧阴离子（O2-）的产生）与对照PMN相比分别提高了75％，37％和24％（P < 0.015）。响应相同的刺激，IFN-γ也分别引起52％，71％和96％的增加（P <0.006）。此外，G-CSF和IFN-γ显着增强了3-4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑（MMT）比色法测定PMNs破坏菌丝的能力。 （分别为P <0.01和<0.05）。不论菌丝的血清调理作用如何，均能达到增强效果，这表明两种细胞因子对调理和非调理菌丝特异的信号途径的上调作用。与单独的细胞因子的作用相比，两种细胞因子的组合在更高的浓度下表现出累加作用（P <0.05）。用蛋白质合成抑制剂对PMN进行预处理表明，IFN-γ通过转录调节激活PMN功能，而G-CSF的作用不需要新的蛋白质。这些体外作用表明，G-CSF和IFN-γ在宿主抵抗曲霉菌菌丝的防御中起调节作用，而与血清调理作用以及细胞因子作为预防和可能治疗浸润性曲霉病的辅助手段无关。

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