The expression of the cytomegalovirus chemokine receptor homolog US28 sequesters biologically active CC chemokines and alters IL-8 production.

The expression of the cytomegalovirus chemokine receptor homolog US28 sequesters biologically active CC chemokines and alters IL-8 production.
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巨细胞病毒趋化因子受体同源物 US28 的表达会隔离具有生物活性的 CC 趋化因子并改变 IL-8 的产生。

DOI:
10.1006/cyto.2002.0874
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发表时间:
2002
期刊:
影响因子:
3.8
通讯作者:
Sedmak,DanielD
Sedmak,DanielD
中科院分区:
医学3区
文献类型:
--
作者:
Randolph-Habecker,Julie-Randoph;Rahill,Brian;Torok-Storb,Beverly;Vieira,Jeffrey;Kolattukudy,PappachanE;Rovin,BradH;Sedmak,DanielD

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我们推测巨细胞病毒(CMV) CC趋化因子受体同源物US28在调节宿主抗病毒防御中起作用。由内源性CC趋化因子MCP-1和RANTES引起的CMV US28缺失突变体(CMVΔUS28)感染成纤维细胞的上清诱导单核细胞趋化。然而,这些趋化因子是从表达US28的cmv感染细胞的上清液中分离出来的。US28也能够隔离外源添加的RANTES。令人惊讶的是,与cmv感染的细胞相比,感染CMVΔUS28的细胞转录和分泌的IL-8(一种CXC趋化因子)水平升高。最后,由于趋化因子是免疫细胞通过内皮迁移的有效介质,我们表征了cmv感染内皮细胞的CC趋化因子结合潜力。我们提出,US28通过隔离内源性和外源性趋化因子,并改变CXC趋化因子IL-8的产生,起到“趋化因子汇”的作用,这表明巨细胞病毒可以显著改变感染细胞周围的炎症环境。
We hypothesized that US28, a cytomegalovirus (CMV) CC chemokine receptor homolog, plays a role in modulating the host antiviral defense. Monocyte chemotaxis was induced by supernatants from fibroblasts infected with a US28 deletion mutant of CMV (CMVΔUS28) due to endogenously produced CC chemokines MCP-1 and RANTES. However, these chemokines were sequestered from the supernatants of CMV-infected cells that did express US28. US28 was also capable of sequestering exogenously added RANTES. Surprisingly, cells infected with CMVΔUS28 transcribed and secreted increased levels IL-8, a CXC chemokine, when compared to CMV-infected cells. Finally, because chemokines are potent mediators of immune cell migration through the endothelium, we characterized the CC chemokine binding potential of CMV-infected endothelial cells. We propose that US28 functions as a ‘chemokine sink’ by sequestering endogenously and exogenously produced chemokines and alters the production of the CXC chemokine IL-8, suggesting that CMV could significantly alter the inflammatory milieu surrounding infected cells.