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Publication : Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis.

First Author  Berri F Year  2013
Journal  PLoS Pathog Volume  9
Issue  3 Pages  e1003229
PubMed ID  23555246 Mgi Jnum  J:196167
Mgi Id  MGI:5486623 Doi  10.1371/journal.ppat.1003229
Citation  Berri F, et al. (2013) Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis. PLoS Pathog 9(3):e1003229
abstractText  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.
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