Gene microarray analysis reveals interleukin-5-dependent transcriptional targets in mouse bone marrow
Gene microarray analysis reveals interleukin-5-dependent transcriptional targets in mouse bone marrow
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DOI：
10.1182/blood-2003-08-2778
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发表时间：
2004-02-01
期刊：
影响因子：
20.3
通讯作者：
Rosenberg, HF
中科院分区：
文献类型：
--
作者：
Byström, J;Wynn, TA;Rosenberg, HF
白细胞介素-5 (IL-5) 是一种造血分化因子，可促进骨髓中祖细胞发育成成熟的嗜酸性粒细胞。我们提出了一项多因素微阵列研究，记录了野生型和 IL-5 缺陷型小鼠骨髓中基线的转录事件以及对曼氏血吸虫感染的反应。通过 4 路减法算法对微阵列数据进行分析，该算法消除了混杂的血吸虫感染的非 IL-5 相关后遗症以及未感染小鼠中基因表达的变化。最突出的发现之一是，仅在产生 IL-5 的感染野生型小鼠中，我们观察到编码经典嗜酸性粒细胞颗粒蛋白（嗜酸性粒细胞过氧化物酶、主要碱性蛋白、核糖核酸酶）以及花生四烯酸 15 脂氧合酶和蛋白酶抑制剂纤溶酶原激活剂抑制剂 2 (PAI-2) 的转录物表达增加了 7 至 40 倍。与此同时，参与分泌蛋白生物合成和颗粒囊泡形成的基因转录增加。有趣的是，我们没有检测到编码嗜酸性粒细胞相关趋化因子受体（CCR1、CCR3）或GATA或CCAAT/增强子结合蛋白（C/EBP）转录因子家族成员的基因表达增加。这些数据表明，小鼠骨髓中的IL-5反应性祖细胞已经明显定向于嗜酸性粒细胞谱系，并且IL-5促进这些定向祖细胞分化成具有可识别和特征性细胞质颗粒和颗粒蛋白的细胞。 (C) 2004 年，美国血液学会。
Interleukin-5 (IL-5) is a hematopoietic differentiation factor that promotes the development of mature eosinophils from progenitors in bone marrow. We present a multifactorial microarray study documenting the transcriptional events in bone marrow of wild-type and IL-5-deficient mice at baseline and in response to infection with Schistosoma mansoni. The microarray data were analyzed by a 4-way subtractive algorithm that eliminated confounding non-IL-5-related sequelae of schistosome infection as well as alterations in gene expression among uninfected mice. Among the most prominent findings, we observed 7- to 40-fold increased expression of transcripts encoding the classic eosinophil granule proteins (eosinophil peroxidase, major basic protein, the ribonucleases) together with arachidonate-15-lipoxygenase and protease inhibitor plasminogen activator inhibitor 2 (PAI-2), in the IL-5-producing, infected wild-type mice only. This was accompanied by increased transcription of genes involved in secretory protein biosynthesis and granule-vesicle formation. Interestingly, we did not detect increased expression of genes encoding eosinophil-related chemokine receptors (CCR1, CCR3) or members of the GATA or CCAAT/enhancer binding protein (C/EBP) transcription factor families. These data suggest that the IL-5-responsive progenitors in the mouse bone marrow are already significantly committed to the eosinophil lineage and that IL-5 promotes differentiation of these committed progenitors into cells with recognizable and characteristic cytoplasmic granules and granule proteins. (C) 2004 by The American Society of Hematology.