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首页> 外文期刊>Infection and immunity >Reduction in superoxide anion secretion and bactericidal activity of neutrophils from aged rats: reversal by the combination of gamma interferon and growth hormone.
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Reduction in superoxide anion secretion and bactericidal activity of neutrophils from aged rats: reversal by the combination of gamma interferon and growth hormone.

机译：老年大鼠中性粒细胞超氧阴离子分泌和杀菌活性的降低：通过γ干扰素和生长激素的组合逆转。

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Polymorphonuclear neutrophils (PMN) from bone marrow of 24-month-old rats kill Escherichia coli less efficiently than PMN from 3-month-old rats. Secretion of O2- and killing of E. coli by PMN from both young and old rats can be significantly augmented by preincubation with either 250 U of gamma interferon (IFN-gamma) or 250 ng of growth hormone (GH) per ml. This priming is specific, because neutralizing monoclonal antibodies against either IFN-gamma or GH completely abrogate the enhanced O2- secretion by PMN from young rats. However, in contrast to PMN from young rats, PMN from aged rats are not primed to kill E. coli by 10-fold-lower concentrations of either IFN-gamma (25 U/ml) or GH (25 ng/ml). To explore the mechanism for the reduction in bacterial killing by PMN from old rats, a syngeneic GH-secreting pituitary cell line (GH3) was implanted in vivo. PMN from GH3-treated aged rats, but not control aged rats, could now be primed in vitro for O2- secretion by IFN-gamma (25 U/ml). Although PMN from aged rats do not respond to the lower doses of either IFN-gamma or GH, the combination of both reagents totally restores the ability of PMN to secrete O2- and to kill E. coli. This synergistic priming is observed with PMN from aged rats, but not with those from young rats, and can be detected when both reagents are added simultaneously or when they are added in either sequence. Furthermore, addition of a monoclonal antibody against either IFN-gamma or GH abrogates the synergism of these two molecules. Collectively, these data identify an important alteration in myeloid cells from aged rodents by showing that their PMN are intrinsically unable to respond to low concentrations of IFN-gamma by secreting O2- and killing bacteria. The results also define a previously unrecognized synergism in PMN from aged animals by showing that GH synergizes with IFN-gamma both in vivo and in vitro to restore these suppressed responses.
机译：24个月大大鼠骨髓中的多形核中性粒细胞（PMN）杀死大肠杆菌的效率低于3个月大大鼠中PMN。通过每毫升250 Uγ干扰素（IFN-γ）或250 ng生长激素（GH）的预培养，可以显着增加幼鼠和老鼠的O2分泌和PMN杀死大肠杆菌。这种引发是特异性的，因为针对IFN-γ或GH的中和性单克隆抗体完全消除了幼鼠PMN增强的O2-分泌。但是，与年轻大鼠的PMN相比，老年大鼠的PMN不会被IFN-γ（25 U / ml）或GH（25 ng / ml）降低10倍的浓度来杀死大肠杆菌。为了探索减少PMN杀死老大鼠细菌的机制，在体内植入了同源的GH分泌垂体细胞系（GH3）。现在，可以通过IFN-γ（25 U / ml）在GH预处理GH3处理的老年大鼠的PMN，但不进行对照的老年大鼠的PMN的O2分泌。尽管来自衰老大鼠的PMN对低剂量的IFN-γ或GH均无反应，但两种试剂的组合可完全恢复PMN分泌O2和杀死大肠杆菌的能力。在老年大鼠的PMN中观察到这种协同启动，而幼鼠的PMN没有观察到，并且当两种试剂同时添加或以任何顺序添加时都可以检测到。而且，添加针对IFN-γ或GH的单克隆抗体消除了这两个分子的协同作用。总体而言，这些数据通过显示它们的PMN本质上无法通过分泌O2-并杀死细菌来响应低浓度的IFN-γ，从而确定了来自老年啮齿动物的髓样细胞的重要改变。该结果还通过显示GH在体内和体外与IFN-γ协同作用来恢复这些抑制的反应，从而确定了老年动物PMN中以前无法识别的协同作用。

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