Loke P'ng, Nair Meera G, Parkinson John, Guiliano David, Blaxter Mark, Allen Judith E
Institute of Cell, Animal and Population Biology, University of Edinburgh, Edinburgh EH9 3JT, UK.
BMC Immunol. 2002 Jul 4;3:7. doi: 10.1186/1471-2172-3-7.
"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 (NeM(phi)) 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 NeM(phi) 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.
“交替活化”的巨噬细胞存在于Th2介导的炎症环境中，如线虫感染和过敏性肺部炎症。部分由于缺乏标志物，这些细胞在体内尚未得到很好的表征，其功能仍然未知。
我们使用线虫感染诱导的小鼠巨噬细胞（NeM(phi)）作为体内来源的交替活化巨噬细胞。通过三种不同但互补的分子方法，我们建立了交替活化巨噬细胞的基因表达谱，并鉴定了在体内受IL-4调节的巨噬细胞基因。首先，通过表达序列标签策略鉴定大量表达的基因。其次，筛选了1176个已知小鼠基因的阵列，以检测野生型或IL-4缺陷小鼠的NeM(phi)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。通过实时RT-PCR分析证实差异表达。
我们的数据表明，体内产生的交替活化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，以前尚未与巨噬细胞相关联，因此本研究提供了关于在Th2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。我们的数据还为线虫感染和过敏所涉及的炎症过程之间的平行关系提供了额外的体内证据。
