The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide.

The impact of breed and tissue compartment on the response of pig macrophages to lipopolysaccharide.
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DOI:
10.1186/1471-2164-14-581
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发表时间:
2013-08-28
期刊:
影响因子:
4.4
通讯作者:
Hume DA
Hume DA
中科院分区:
生物学2区
文献类型:
--
作者:
Kapetanovic R;Fairbairn L;Downing A;Beraldi D;Sester DP;Freeman TC;Tuggle CK;Archibald AL;Hume DA

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家猪(Sus scrofa)的基因组草图最近已经发表,允许对转录组进行精细分析。据报道,猪品种对传染病的抵抗力不同。在这项研究中,我们检查先天免疫细胞中的基因表达是否存在相应的差异。我们证明,巨噬细胞可以从猪的三个不同隔室(肺、血液和骨髓)中收获,冷冻保存,随后在CSF-1中回收和分化。我们已经进行了表面标记分析和基因表达谱的巨噬细胞从这些车厢,比较25个动物从五个不同的品种和他们的反应脂多糖。结果提供了肺泡巨噬细胞(AM)与单核细胞衍生的(MDM)和骨髓衍生的巨噬细胞(BMDM)之间的明显区别。特别是,肺巨噬细胞高水平表达生长因子FLT 1及其配体VEGFA,表明了不同的生长调节途径。相对较少的基因表现出品种特异性差异表达,特别是肺泡巨噬细胞中的CXCR 2和CD 302。相比之下,品种内猪之间存在大量个体间差异,主要影响注释为参与免疫反应的基因。猪巨噬细胞在其巨噬细胞表达和LPS诱导的基因组方面比小鼠更接近人类。未来的研究将解决巨噬细胞基因表达的个体间变异是否是可遗传的,并可能形成抗病选择性育种的基础。
The draft genome of the domestic pig (Sus scrofa) has recently been published permitting refined analysis of the transcriptome. Pig breeds have been reported to differ in their resistance to infectious disease. In this study we examine whether there are corresponding differences in gene expression in innate immune cells We demonstrate that macrophages can be harvested from three different compartments of the pig (lungs, blood and bone-marrow), cryopreserved and subsequently recovered and differentiated in CSF-1. We have performed surface marker analysis and gene expression profiling on macrophages from these compartments, comparing twenty-five animals from five different breeds and their response to lipopolysaccharide. The results provide a clear distinction between alveolar macrophages (AM) and monocyte-derived (MDM) and bone-marrow-derived macrophages (BMDM). In particular, the lung macrophages express the growth factor, FLT1 and its ligand, VEGFA at high levels, suggesting a distinct pathway of growth regulation. Relatively few genes showed breed-specific differential expression, notably CXCR2 and CD302 in alveolar macrophages. In contrast, there was substantial inter-individual variation between pigs within breeds, mostly affecting genes annotated as being involved in immune responses. Pig macrophages more closely resemble human, than mouse, in their set of macrophage-expressed and LPS-inducible genes. Future research will address whether inter-individual variation in macrophage gene expression is heritable, and might form the basis for selective breeding for disease resistance.
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