tetano
Editor, Senior Moderator
Am J Respir Cell Mol Biol. 2011 Feb 17. [Epub ahead of print]
Impact of Endogenous Protein C on Pulmonary Coagulation and Injury During Lethal H1N1 Influenza in Mice.
Schouten M, de Boer JD, van der Sluijs KF, Roelofs JJ, van 't Veer C, Levi M, Esmon CT, van der Poll T.
Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands; Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands.
Abstract
Influenza accounts for 5-10% of community-acquired pneumonia cases and is a major cause of mortality. Sterile and bacterial lung injury are associated with procoagulant and inflammatory derangements in the lungs and downregulation of the protein C (PC) pathway has been correlated to disease severity and mortality in severe bacterial pneumonia and sepsis. Also during lethal influenza pneumonia, pulmonary and systemic coagulation are activated, which can be attenuated by the administration of recombinant activated (A)PC. We here determined the role of endogenous PC in lethal H1N1 influenza A infection. Male C57BL/6 mice pretreated with an inhibitory monoclonal antibody directed against murine PC or a control antibody were intranasally infected with a lethal dose of a mouse adapted H1N1 influenza A strain. Mice were sacrificed at 48 or 96 hours after infection, after which lungs and bronchoalveolar lavage fluid were harvested, or observed for up to 9 days. Anti-PC antibody treatment aggravated pulmonary activation of coagulation as compared to control antibody treatment as reflected by increased lung concentrations of thrombin-antithrombin complexes and fibrin degradation products, as well as intravascular thrombus formation. Anti-PC antibody treatment aggravated lung histopathology but lowered bronchoalveolar neutrophil influx and total protein levels and delayed mortality. In conclusion, endogenous PC has strong effects on the host response to lethal influenza A infection, on the one hand inhibiting pulmonary coagulopathy and inflammation, but on the other hand facilitating neutrophil influx and protein leak and accelerating mortality.
PMID: 21330465 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21330465
Impact of Endogenous Protein C on Pulmonary Coagulation and Injury During Lethal H1N1 Influenza in Mice.
Schouten M, de Boer JD, van der Sluijs KF, Roelofs JJ, van 't Veer C, Levi M, Esmon CT, van der Poll T.
Center for Experimental and Molecular Medicine (CEMM), University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands; Center for Infection and Immunity Amsterdam (CINIMA), University of Amsterdam, Academic Medical Center, Amsterdam, Netherlands.
Abstract
Influenza accounts for 5-10% of community-acquired pneumonia cases and is a major cause of mortality. Sterile and bacterial lung injury are associated with procoagulant and inflammatory derangements in the lungs and downregulation of the protein C (PC) pathway has been correlated to disease severity and mortality in severe bacterial pneumonia and sepsis. Also during lethal influenza pneumonia, pulmonary and systemic coagulation are activated, which can be attenuated by the administration of recombinant activated (A)PC. We here determined the role of endogenous PC in lethal H1N1 influenza A infection. Male C57BL/6 mice pretreated with an inhibitory monoclonal antibody directed against murine PC or a control antibody were intranasally infected with a lethal dose of a mouse adapted H1N1 influenza A strain. Mice were sacrificed at 48 or 96 hours after infection, after which lungs and bronchoalveolar lavage fluid were harvested, or observed for up to 9 days. Anti-PC antibody treatment aggravated pulmonary activation of coagulation as compared to control antibody treatment as reflected by increased lung concentrations of thrombin-antithrombin complexes and fibrin degradation products, as well as intravascular thrombus formation. Anti-PC antibody treatment aggravated lung histopathology but lowered bronchoalveolar neutrophil influx and total protein levels and delayed mortality. In conclusion, endogenous PC has strong effects on the host response to lethal influenza A infection, on the one hand inhibiting pulmonary coagulopathy and inflammation, but on the other hand facilitating neutrophil influx and protein leak and accelerating mortality.
PMID: 21330465 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21330465