In vitro activation of mouse neutrophils by recombinant human interferon-gamma: Increased phagocytosis and release of reactive oxygen species and pro-inflammatory cytokines

In vitro activation of mouse neutrophils by recombinant human interferon-gamma: Increased phagocytosis and release of reactive oxygen species and pro-inflammatory cytokines
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DOI:
10.1016/j.intimp.2013.12.010
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发表时间:
2014-02-01
影响因子:
5.6
通讯作者:
Mantovani, B.
Mantovani, B.
中科院分区:
医学2区
文献类型:
--
作者:
Marchi, L. F.;Sesti-Costa, R.;Mantovani, B.

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在这里,我们研究了IFN-γ在体外调节小鼠中性粒细胞功能的能力。在IFN-γ存在下孵育的中性粒细胞对酵母聚糖、调理酵母聚糖或IgG和卵清蛋白的沉淀免疫复合物的吞噬作用增强。IFN-γ的作用是剂量依赖性的,初始反应为10 U/ml,最大反应为150 U/ml;需要孵育2 h才能达到最佳反应水平。这些刺激还可以诱导IFN-γ预处理的嗜中性粒细胞释放活性氧物质(ROS),例如超氧阴离子、过氧化氢和次氯酸,以及颗粒溶酶体酶和促炎细胞因子TNF-α和IL-6。我们发现Fc γ R、dectin-1和补体受体(CR)的表达增加与这些细胞中的这些效应相关。IFN-γ对呼吸爆发的增强作用被发现与NADPH氧化酶的gp 91(phox)和p47(phox)亚基的上调相关,如通过它们的mRNA水平所测量的。IFN-γ对吞噬作用和ROS释放的增强作用可能不仅与入侵微生物的有效杀死有关,而且还可能对邻近细胞产生氧化应激,导致可能的炎症作用,这也可能受到促炎细胞因子TNF-α和IL-6释放的影响。(C)2013 Elsevier B. V.保留所有权利。
Here, we investigated the ability of IFN-gamma to modulate the functions of mouse neutrophils in vitro. Neutrophils incubated in the presence of IFN-gamma showed enhanced phagocytosis in response to zymosan, opsonized zymosan or precipitated immune complexes of IgG and ovalbumin. The effect of IFN-gamma was dose-dependent with an initial response at 10 U/ml and a maximal response at 150 U/ml; 2 h of incubation were required to reach the optimal response level. These stimuli can also induce IFN-gamma-pretreated neutrophils to release reactive oxygen species (ROS), such as superoxide anion, hydrogen peroxide and hypochlorous acid, as well as granule lysosomal enzymes and the pro-inflammatory cytokines TNF-alpha and IL-6. We found that increased expression of Fc gamma R, dectin-1 and complement receptors (CRs) correlated with these effects in these cells. The enhancing effect of IFN-gamma on the respiratory burst was found to be associated with up-regulation of the gp91(phox) and p47(phox) subunits of NADPH oxidase, as measured by their mRNA levels. The enhancing effect of IFN-gamma on phagocytosis and ROS release may not only be relevant for the efficient killing of invading microorganisms, but may also produce oxidative stress on adjacent cells, resulting in a possible inflammatory role that could also be favored by the liberation of the pro-inflammatory cytokines TNF-alpha and IL-6. (C) 2013 Elsevier B.V. All rights reserved.