美國斯克里普斯研究所的科學(xué)家最新研究發(fā)現(xiàn)了流感病毒使感染者病重甚至死亡的機(jī)理,。相關(guān)研究發(fā)表在9月16日出版的《細(xì)胞》雜志上。
研究人員將這種流感致死的免疫過程稱為“細(xì)胞因子風(fēng)暴”,，可以預(yù)測病毒感染過程的發(fā)病率和死亡率，其被認(rèn)為是1918-1919 年間世界大流感和近來豬流感,、禽流感爆發(fā)的主因。
在這篇論文中,，研究人員利用遺傳學(xué)和化學(xué)手段研究細(xì)胞表面受體S1P1,。他們意外地發(fā)現(xiàn)當(dāng)控制血管壁內(nèi)皮細(xì)胞的S1P1受體時(shí)，會(huì)影響細(xì)胞因子的釋放,。而之前科學(xué)家猜想細(xì)胞因子釋放是通過位于肺部的受病毒侵染細(xì)胞發(fā)生的,。
NIH的詹姆斯M ·安德森博士表示,，此項(xiàng)工作極大地提高了人們對(duì)“細(xì)胞因子風(fēng)暴”生物基礎(chǔ)的認(rèn)識(shí)，打開了研發(fā)這種致命疾病新療法的大門,。（生物谷 Bioon.com）
doi: 10.1016/j.cell.2011.08.015
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Endothelial Cells Are Central Orchestrators of Cytokine Amplification during Influenza Virus Infection
John R. Teijaro, Kevin B. Walsh, Stuart Cahalan, Daniel M. Fremgen, Edward Roberts, Fiona Scott, Esther Martinborough, Robert Peach, Michael B.A. Oldstone, Hugh Rosen
Cytokine storm during viral infection is a prospective predictor of morbidity and mortality, yet the cellular sources remain undefined. Here, using genetic and chemical tools to probe functions of the S1P1 receptor, we elucidate cellular and signaling mechanisms that are important in initiating cytokine storm. Whereas S1P1 receptor is expressed on endothelial cells and lymphocytes within lung tissue, S1P1 agonism suppresses cytokines and innate immune cell recruitment in wild-type and lymphocyte-deficient mice, identifying endothelial cells as central regulators of cytokine storm. Furthermore, our data reveal immune cell infiltration and cytokine production as distinct events that are both orchestrated by endothelial cells. Moreover, we demonstrate that suppression of early innate immune responses through S1P1 signaling results in reduced mortality during infection with a human pathogenic strain of influenza virus. Modulation of endothelium with a specific agonist suggests that diseases in which amplification of cytokine storm is a significant pathological component could be chemically tractable.
