Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis.
Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis.
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DOI：
10.1371/journal.ppat.1003229
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发表时间：
2013-03
期刊：
影响因子：
6.7
通讯作者：
Riteau B
中科院分区：
文献类型：
--
作者：
Berri F;Rimmelzwaan GF;Hanss M;Albina E;Foucault-Grunenwald ML;Lê VB;Vogelzang-van Trierum SE;Gil P;Camerer E;Martinez D;Lina B;Lijnen R;Carmeliet P;Riteau B
肺部的有害炎症是严重流感病毒感染的标志。内皮细胞是细胞因子扩增的来源，尽管该过程的机制尚不清楚。在这里，使用组合的药理学和基因缺失的方法，我们表明，纤溶酶原控制肺部炎症和感染A/PR/8/34，高致病性H5 N1和2009年大流行性H1N1病毒的发病机制。病毒复制的减少不是观察到的效果的原因。然而，纤溶酶原的主要靶点纤维蛋白原的药理学消耗逆转了纤溶酶原缺陷小鼠或用纤溶酶原介导的纤维蛋白溶解抑制剂治疗的小鼠的疾病抗性。因此，纤溶酶原有助于肺的有害炎症，并且局部纤维蛋白凝块形成可能涉及宿主对流感病毒感染的防御。我们的研究表明，止血系统可能会探索新的治疗流感。包括H5 N1禽流感病毒在内的流感病毒继续对公共卫生构成重大威胁。现有治疗流感的抗病毒药物在有限程度上有效，耐药病毒的出现可能进一步破坏其使用。与流感相关的症状是由病毒在呼吸道和宿主免疫反应中的复制引起的。在这里，我们报告说，纤溶系统的一个分子，纤溶酶原，有助于流感引起的炎症。抑制纤溶酶原的作用可保护小鼠免受严重流感感染，包括由H5 N1和H1N1大流行性2009病毒引起的感染，并且可能是治疗流感的有希望的新策略。
Detrimental inflammation of the lungs is a hallmark of severe influenza virus infections. Endothelial cells are the source of cytokine amplification, although mechanisms underlying this process are unknown. Here, using combined pharmacological and gene-deletion approaches, we show that plasminogen controls lung inflammation and pathogenesis of infections with influenza A/PR/8/34, highly pathogenic H5N1 and 2009 pandemic H1N1 viruses. Reduction of virus replication was not responsible for the observed effect. However, pharmacological depletion of fibrinogen, the main target of plasminogen reversed disease resistance of plasminogen-deficient mice or mice treated with an inhibitor of plasminogen-mediated fibrinolysis. Therefore, plasminogen contributes to the deleterious inflammation of the lungs and local fibrin clot formation may be implicated in host defense against influenza virus infections. Our studies suggest that the hemostatic system might be explored for novel treatments against influenza. Influenza viruses, including H5N1 bird influenza viruses continue to form a major threat for public health. Available antiviral drugs for the treatment of influenza are effective to a limited extent and the emergence of resistant viruses may further undermine their use. The symptoms associated with influenza are caused by replication of the virus in the respiratory tract and the host immune response. Here, we report that a molecule of the fibrinolytic system, plasminogen, contributes to inflammation caused by influenza. Inhibiting the action of plasminogen protected mice from severe influenza infections, including those caused by H5N1 and H1N1 pandemic 2009 viruses and may be a promising novel strategy to treat influenza.
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影响因子：
2.4
作者：
Couacy-Hymann, E.;Danho, T.;Cattoli, G.
通讯作者：
Cattoli, G.
影响因子：
5.4
作者：
Goto, H;Wells, K;Kawaoka, Y
通讯作者：
Kawaoka, Y
影响因子：
2.7
作者：
LeBouder, Fanny;Khoufache, Khaled;Riteau, Beatrice
通讯作者：
Riteau, Beatrice
影响因子：
20.3
作者：
O'Connell, Paul A.;Surette, Alexi P.;Waisman, David M.
通讯作者：
Waisman, David M.
DOI：
10.1126/science.1177127
发表时间：
2009-07-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Munster VJ;de Wit E;van den Brand JM;Herfst S;Schrauwen EJ;Bestebroer TM;van de Vijver D;Boucher CA;Koopmans M;Rimmelzwaan GF;Kuiken T;Osterhaus AD;Fouchier RA
通讯作者：
Fouchier RA