IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype.
IL-4 dependent alternatively-activated macrophages have a distinctive in vivo gene expression phenotype.
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DOI：
10.1186/1471-2172-3-7
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发表时间：
2002-07-04
期刊：
影响因子：
3
通讯作者：
Allen JE
中科院分区：
文献类型：
--
作者：
Loke P;Nair MG;Parkinson J;Guiliano D;Blaxter M;Allen JE
“替代性激活的”巨噬细胞存在于Th 2介导的炎症环境中，如线虫感染和过敏性肺部炎症。部分由于缺乏标记物，这些细胞尚未在体内得到很好的表征，它们的功能仍然未知。我们已经使用线虫感染引起的小鼠巨噬细胞（NeMφ）作为体内衍生的替代活化巨噬细胞的来源。使用三种不同但互补的分子方法，我们已经建立了一个基因表达谱的替代激活的巨噬细胞和确定的巨噬细胞基因，在体内调节IL-4。首先，通过表达序列标签策略鉴定大量表达的基因。第二，筛选了1176个已知小鼠基因的阵列，用于来自野生型或IL-4缺陷型小鼠的NeMφ之间的差异表达。第三，筛选消减文库以鉴定新的IL-4依赖性巨噬细胞基因。通过真实的时间RT-PCR分析证实差异表达。我们的数据表明，体内产生的替代活化的巨噬细胞具有与迄今为止描述的任何巨噬细胞群体不同的基因表达谱。我们鉴定的几个基因，包括那些表达最丰富的基因，以前没有与巨噬细胞相关，因此这项研究提供了关于Th 2介导的慢性炎症环境中发现的巨噬细胞表型的独特新信息。我们的数据还提供了额外的体内证据，在线虫感染和过敏所涉及的炎症过程之间的相似之处。
"Alternatively-activated" macrophages are found in Th2-mediated inflammatory settings such as nematode infection and allergic pulmonary inflammation. Due in part to a lack of markers, these cells have not been well characterized in vivo and their function remains unknown. We have used murine macrophages elicited by nematode infection (NeMφ) as a source of in vivo derived alternatively activated macrophages. Using three distinct yet complementary molecular approaches we have established a gene expression profile of alternatively activated macrophages and identified macrophage genes that are regulated in vivo by IL-4. First, genes abundantly expressed were identified by an expressed sequence tag strategy. Second, an array of 1176 known mouse genes was screened for differential expression between NeMφ from wild type or IL-4 deficient mice. Third, a subtractive library was screened to identify novel IL-4 dependent macrophage genes. Differential expression was confirmed by real time RT-PCR analysis. Our data demonstrate that alternatively activated macrophages generated in vivo have a gene expression profile distinct from any macrophage population described to date. Several of the genes we identified, including those most abundantly expressed, have not previously been associated with macrophages and thus this study provides unique new information regarding the phenotype of macrophages found in Th2-mediated, chronic inflammatory settings. Our data also provide additional in vivo evidence for parallels between the inflammatory processes involved in nematode infection and allergy.