Macrophages have vital roles in innate immunity by modulating the inflammatory response via their ability to alter their phenotype from pro-inflammatory (M1) to anti-inflammatory (M2). Aging increases activation of the innate immune system, and macrophage numbers increase in the aged liver. Since macrophages also produce free radical molecules, they are a potential source of age-related oxidative injury in the liver. This study evaluated macrophage phenotype in the aged liver and whether the increase in the number of macrophages with aging is associated with enhanced hepatic oxidative stress. Hepatic macrophage phenotype and oxidative stress were evaluated 2 days after a single intraperitoneal injection of saline or gadolinium chloride (GdCl3, 10 mg/kg) in young (6 months) and aged (24 months) Fischer 344 rats. GdCl3 has been shown to decrease the expression of macrophage-specific markers and impair macrophage phagocytosis in the liver. Saline-treated aged rats demonstrated greater numbers of both M1 (HO-1+/iNOS+) and M2 (HO-1+/CD163+) macrophages, without evidence of a phenotypic shift. GdCl3 did not alter levels of dihydroethidium fluorescence or malondialdehyde, suggesting that macrophages are not a major contributor to steady-state levels of oxidative stress. However, GdCl3 decreased M1 and M2 macrophage markers in both age groups, an effect that was attenuated in aged rats. In old animals, GdCl3 decreased iNOS expression to a greater extent than HO-1 or CD163. These results suggest a novel effect of aging on macrophage biology and that GdCl3 shifts hepatic macrophage polarization to the M2 phenotype in aged animals.

中文翻译：

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衰老导致M1和M2肝巨噬细胞蓄积，并对氯化a的反应不同。

巨噬细胞通过改变其表型从促炎（M1）变为抗炎（M2）的能力来调节炎症反应，从而在先天免疫中起着至关重要的作用。衰老会增加先天免疫系统的激活，而衰老的肝脏中巨噬细胞的数量会增加。由于巨噬细胞还产生自由基分子，因此它们是肝脏中与年龄相关的氧化损伤的潜在来源。这项研究评估了衰老肝脏中巨噬细胞的表型，以及随着衰老而增加的巨噬细胞数量是否与增强的肝氧化应激有关。在年轻（6个月）和年龄（24个月）的Fischer 344大鼠中，单次腹膜内注射盐水或氯化g（GdCl3，10 mg / kg）2天后，评估肝巨噬细胞表型和氧化应激。已显示GdCl3会降低肝脏中巨噬细胞特异性标志物的表达并损害巨噬细胞的吞噬作用。盐水处理的老年大鼠表现出更大数量的M1（HO-1 + / iNOS +）和M2（HO-1 + / CD163 +）巨噬细胞，而没有表型转移的证据。GdCl3不会改变二氢乙啶荧光或丙二醛的水平，这表明巨噬细胞不是氧化应激稳态水平的主要贡献者。然而，GdCl3降低了两个年龄组中的M1和M2巨噬细胞标志物，这种作用在衰老大鼠中减弱了。在老年动物中，GdCl3降低iNOS表达的程度大于HO-1或CD163。这些结果表明衰老对巨噬细胞生物学产生了新的影响，而GdCl3将衰老动物的肝巨噬细胞极化转变为M2表型。