Bone marrow-derived macrophages from BALB/c and C57BL/6 mice fundamentally differ in their respiratory chain complex proteins, lysosomal enzymes and components of antioxidant stress systems
Bone marrow-derived macrophages from BALB/c and C57BL/6 mice fundamentally differ in their respiratory chain complex proteins, lysosomal enzymes and components of antioxidant stress systems
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DOI：
10.1016/j.jprot.2014.03.027
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发表时间：
2014-05-30
影响因子：
3.3
通讯作者：
Voelker, Uwe
中科院分区：
文献类型：
--
作者：
Depke, Maren;Breitbach, Katrin;Voelker, Uwe
巨噬细胞是先天免疫系统的重要组成部分，对于感染早期阶段的病原体消除至关重要。我们之前观察到，与 BALB/c 小鼠的骨髓源性巨噬细胞 (BMM) 相比，C57BL/6 小鼠的骨髓源性巨噬细胞 (BMM) 对鼻疽伯克霍尔德氏菌的杀伤活性增强。当细胞用 IFN-γ 处理时，这种效应尤其明显。为了阐明可以解释这些不同杀菌作用的机制，在标准化无血清条件下对未经处理和 IFN-gamma 处理的 BALB/c 和 C57BL/6 BMM 进行了比较性蛋白质组和转录组组合分析。我们发现细胞氧化和抗氧化应激系统的基因表达/蛋白质丰度存在差异。参与氧化剂分子生成和吞噬体功能（呼吸链 ATP 酶、溶酶体酶、组织蛋白酶）的基因/蛋白质在 C57B116 BMM 中主要表达更高/更丰富。 C57BL/6 BMM 中参与缓解氧化应激的成分（过氧化还原蛋白、线粒体超氧化物歧化酶）也更丰富。因此，C57BL/6 BMM 似乎更好地配备了可能有利于对抗吞噬病原体的细胞系统。同时，C57BL/6 BMM 得到了很好的保护，免受氧化爆发。我们假设这些变异共同决定了在许多感染模型中观察到的 BALB/c 和 C57BL/6 小鼠之间的耐药性差异。 生物学意义在这项研究中，我们对源自两种近交系小鼠品系的 BMM 进行了组合转录组和蛋白质组分析，这两种小鼠品系经常用于宿主-病原体相互作用研究领域的研究。研究发现 BALB/c 和 C57BL/6 BMM 之间的菌株差异主要源于不同的蛋白质丰度水平，而不是不同的基因表达。呼吸链复合物和溶酶体蛋白丰度的差异以及属于各种抗氧化应激系统的成分的差异调节有助于解释小鼠品系之间长期以来已知的差异，即它们在几种感染模型中的不同易感性。 (C) 2014 Elsevier B.V. 保留所有权利。
Macrophages are essential components of the innate immune system and crucial for pathogen elimination in early stages of infection. We previously observed that bone marrow-derived macrophages (BMMs) from C57BL/6 mice exhibited increased killing activity against Burkholderia pseudomallei compared to BMMs from BALB/c mice. This effect was particularly pronounced when cells were treated with IFN-gamma. To unravel mechanisms that could explain these distinct bactericidal effects, a comparative combined proteome and transcriptome analysis of untreated and IFN-gamma treated BALB/c and C57BL/6 BMMs under standardized serum-free conditions was carried out. We found differences in gene expression/protein abundance belonging to cellular oxidative and antioxidative stress systems. Genes/proteins involved in the generation of oxidant molecules and the function of phagosomes (respiratory chain ATPase, lysosomal enzymes, cathepsins) were predominantly higher expressed/more abundant in C57B116 BMMs. Components involved in alleviation of oxidative stress (peroxiredoxin, mitochondrial superoxide dismutase) were more abundant in C57BL/6 BMMs as well. Thus, C57BL/6 BMMs seemed to be better equipped with cellular systems that may be advantageous in combating engulfed pathogens. Simultaneously, C57BL/6 BMMs were well protected from oxidative burst. We assume that these variations co-determine differences in resistance between BALB/c and C57BL/6 mice observed in many infection models.Biological significanceIn this study we performed combined transcriptome and proteome analyses on BMMs derived from two inbred mouse strains that are frequently used for studies in the field of host-pathogen interaction research. Strain differences between BALB/c and C57BL/6 BMMs were found to originate mainly from different protein abundance levels rather than from different gene expression. Differences in abundance of respiratory chain complexes and lysosomal proteins as well as differential regulation of components belonging to various antioxidant stress systems help to explain long-known differences between the mouse strains concerning their different susceptibility in several infection models. (C) 2014 Elsevier B.V. All rights reserved.