Expression of interleukin-5-and granulocyte macrophage-colony-stimulating factor-responsive genes in blood and airway eosinophils
Expression of interleukin-5-and granulocyte macrophage-colony-stimulating factor-responsive genes in blood and airway eosinophils
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DOI：
10.1165/rcmb.2003-0234oc
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发表时间：
2004-05-01
影响因子：
6.4
通讯作者：
Bertics, PJ
中科院分区：
文献类型：
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作者：
Bates, ME;Liu, LY;Bertics, PJ
由于白细胞介素(IL)-5家族细胞因子是嗜酸性粒细胞发育、募集和激活的关键调节因子，本研究旨在鉴定嗜酸性粒细胞中由这些细胞因子诱导的蛋白。利用寡核苷酸微阵列技术，许多转录本被鉴定为对IL-5和粒细胞巨噬细胞集落刺激因子（G - csf）均有应答，但没有转录本受到一种细胞因子的显著影响。在体外刺激人血嗜酸性粒细胞后，几种基因产物的表达增加，包括IL-3受体α亚基、淋巴毒素β、Pim-1和细胞周期蛋白D3。考虑到过敏症患者的支气管肺泡灌洗液中提取的嗜酸性粒细胞在分离前暴露于气道中的IL-5或GM-CSF中，我们验证了IL-5和GM-CSF反应基因在气道嗜酸性粒细胞中相对于在血细胞中的表达上调的假设。气道嗜酸性粒细胞在细胞表面表达IL-3受体a亚基CD44、CD25和CD66e，提示这些蛋白可能是气道嗜酸性粒细胞被IL-5家族细胞因子激活的标志。IL-5和GM-CSF诱导的其他基因在气道嗜酸性粒细胞中的蛋白表达水平与循环中的对应基因（即淋巴毒素β和CD24）相似或降低。这些研究已经确定了IL-5和GM-CSF在人嗜酸性粒细胞中的几个转录靶点，并表明许多蛋白质产物对气道嗜酸性粒细胞的反应性至关重要。
Because interleukin (IL)-5 family cytokines are critical regulators of eosinophil development, recruitment, and activation, this study was initiated to identify proteins induced by these cytokines in eosinophils. Using oligonucleotide microarrays, numerous transcripts were identified as responsive to both IL-5 and granulocyte macrophage-colony-stimulating factor (G M-CSF), but no transcripts were markedly affected by one cytokine and not the other. Expression of several gene products were seen to be increased following in vitro stimulation of human blood eosinophils, including the IL-3 receptor alpha subunit, lymphotoxin beta, Pim-1, and cyclin D3. Given that eosinophils recovered from the bronchoalveolar lavage fluid of allergic patients after antigen challenge are exposed to IL-5 or GM-CSF in the airway prior to isolation, the hypothesis was tested that selected IL-5- and GM-CSF-responsive genes are upregulated in airway eosinophils relative to the expression in blood cells. Airway eosinophils displayed greater cell surface expression of the IL-3 receptor a subunit, CD44, CD25, and CD66e, suggesting that these proteins may be markers of eosinophil activation by IL-5 family cytokines in airway eosinophils. Other genes that were induced by both IL-5 and GM-CSF showed protein expression at similar or decreased levels in airway eosinophils relative to their circulating counterparts (i.e., lymphotoxin beta and CD24). These studies have identified several transcriptional targets of IL-5 and GM-CSF in human eosinophils and suggest that a number of protein products are critical to the responsiveness of airway eosinophils.