Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs
Neutrophils alter the inflammatory milieu by signal-dependent translation of constitutive messenger RNAs
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DOI：
10.1073/pnas.0401901101
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发表时间：
2004-05-04
影响因子：
11.1
通讯作者：
Zimmerman, GA
中科院分区：
文献类型：
--
作者：
Lindemann, SW;Yost, CC;Zimmerman, GA
中性粒细胞是先天免疫系统的关键效应细胞，其在炎症中表达新基因产物的机制在很大程度上尚不清楚。我们发现，当它们被激活时，它们会迅速翻译结构性的mRNAs，这是一种以前未被识别的反应。其中一种不需要转录就能合成的蛋白质是可溶性IL-6受体α，它可以移位到内皮细胞，并诱导暂时转变为单核白细胞募集。它的合成由一个专门的翻译控制途径调节，该途径被雷帕霉素抑制，雷帕霉素是一种细菌大环内酯，对移植、炎症综合征和肿瘤具有治疗效果。激活的中性粒细胞的信号依赖翻译可能是炎症环境改变的关键机制和治疗靶点。
The mechanisms by which neutrophils, key effector cells of the innate immune system, express new gene products in inflammation are largely uncharacterized. We found that they rapidly translate constitutive mRNAs when activated, a previously unrecognized response. One of the proteins synthesized without a requirement for transcription is the soluble IL-6 receptor alpha, which translocates to endothelial cells and induces a temporal switch to mononuclear leukocyte recruitment. Its synthesis is regulated by a specialized translational control pathway that is inhibited by rapamycin, a bacterial macrolide with therapeutic efficacy in transplantation, inflammatory syndromes, and neoplasia. Signal-dependent translation in activated neutrophils may be a critical mechanism for alteration of the inflammatory milieu and a therapeutic target.