Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide
Pig Bone Marrow-Derived Macrophages Resemble Human Macrophages in Their Response to Bacterial Lipopolysaccharide
复制标题
DOI：
10.4049/jimmunol.1102649
复制
发表时间：
2012-04-01
影响因子：
4.4
通讯作者：
Hume, David A.
中科院分区：
文献类型：
--
作者：
Kapetanovic, Ronan;Fairbairn, Lynsey;Hume, David A.
在巨噬细胞集落刺激因子（CSF - 1）中培养的小鼠骨髓来源的巨噬细胞（BMDM）已广泛用于巨噬细胞生物学以及对Toll样受体（TLR）激动剂反应的研究。我们研究了是否可以使用人重组CSF - 1从家猪中获得类似的细胞，以及猪巨噬细胞是否可能代表一种更好的人类巨噬细胞生物学模型。在人重组CSF - 1存在的情况下，将猪骨髓细胞培养5 - 7天，产生了一个纯的BMDM群体，其表达常见的巨噬细胞标志物（CD14、CD16和CD172a），是有效的吞噬细胞，并在对脂多糖（LPS）反应时产生肿瘤坏死因子（TNF）。猪BMDM可以从经过冷冻和复苏的骨髓细胞中产生，这样就可以对来自单只动物的样本进行多次实验。使用Affymetrix微阵列分析了来自对LPS有反应的远交系动物的猪BMDM中的基因表达。可诱导和可抑制基因的时间级联反应与人类巨噬细胞的已知反应比与小鼠巨噬细胞的更为相似，与人类一样，参与色氨酸代谢（吲哚胺2,3 - 双加氧酶（IDO）、犬尿氨酸（KYN））、淋巴细胞趋化因子（趋化因子（C - C基序）配体20（CCL20）、趋化因子（C - X - C基序）配体9（CXCL9）、趋化因子（C - X - C基序）配体11（CXCL11）、趋化因子（C - X - C基序）配体13（CXCL13））以及维生素D3转化酶（Cyp27B1）的基因受到调控。相反，与已发表的人类巨噬细胞研究相同，猪BMDM不会强烈诱导参与精氨酸代谢的基因，也不会产生一氧化氮（NO）。这些结果确立了猪BMDM作为研究巨噬细胞转录调控的一种可选的易于处理的模型。《免疫学杂志》，2012年，188卷：3382 - 3394页。
Mouse bone marrow-derived macrophages (BMDM) grown in M-CSF (CSF-1) have been used widely in studies of macrophage biology and the response to TLR agonists. We investigated whether similar cells could be derived from the domestic pig using human rCSF-1 and whether porcine macrophages might represent a better model of human macrophage biology. Cultivation of pig bone marrow cells for 5-7 d in presence of human rCSF-1 generated a pure population of BMDM that expressed the usual macrophage markers (CD14, CD16, and CD172a), were potent phagocytic cells, and produced TNF in response to LPS. Pig BMDM could be generated from bone marrow cells that had been stored frozen and thawed so that multiple experiments can be performed on samples from a single animal. Gene expression in pig BMDM from outbred animals responding to LPS was profiled using Affymetrix microarrays. The temporal cascade of inducible and repressible genes more closely resembled the known responses of human than mouse macrophages, sharing with humans the regulation of genes involved in tryptophan metabolism (IDO, KYN), lymphoattractant chemokines (CCL20, CXCL9, CXCL11, CXCL13), and the vitamin D3-converting enzyme, Cyp27B1. Conversely, in common with published studies of human macrophages, pig BMDM did not strongly induce genes involved in arginine metabolism, nor did they produce NO. These results establish pig BMDM as an alternative tractable model for the study of macrophage transcriptional control. The Journal of Immunology, 2012, 188: 3382-3394.