Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia

Cellular and Molecular Immunology

Volumn 13, Issue 4, 2016, Pages 432-442

  Yang, Yan ^a   Tang, Hong ^a,b  

^a WUHAN INSTITUTE OF VIROLOGY   (China)

^b INSTITUTE PASTEUR OF SHANGHAI   (China)

Author keywords

Anticoagulant; coagulation; inflammation; influenza A virus

Indexed keywords

AMINOCAPROIC ACID; INTERCELLULAR ADHESION MOLECULE 1; PADGEM PROTEIN; THROMBIN; THROMBOPLASTIN; VON WILLEBRAND FACTOR;

BLOOD CLOTTING; BLOOD CLOTTING DISORDER; DISEASE ASSOCIATION; DISEASE SEVERITY; DISSEMINATED INTRAVASCULAR CLOTTING; ENDOTHELIUM CELL; FIBRINOLYSIS; HEMOSTASIS; HOMEOSTASIS; HUMAN; IMMUNE RESPONSE; INFLAMMATION; INFLUENZA A; NONHUMAN; PARTIAL THROMBOPLASTIN TIME; PATHOGENESIS; PNEUMONIA; POLYMERIZATION; PROTEIN EXPRESSION; PROTHROMBIN TIME; REVIEW; SUPERINFECTION; ANIMAL; BLOOD; COMPLICATION; INFLUENZA; METABOLISM; PATHOLOGY;

ANIMALS; BLOOD COAGULATION; ENDOTHELIAL CELLS; FIBRINOLYSIS; HUMANS; INFLAMMATION; INFLUENZA, HUMAN; PNEUMONIA;

EID: 84977552315     PISSN: 16727681     EISSN: None     Source Type: Journal    
DOI: 10.1038/cmi.2016.1     Document Type: Review

References (155)

1. Tong S, Zhu X, Li Y, Shi M, Zhang J, Bourgeois M et al. New world bats harbor diverse influenza A viruses. PLoS Pathog 2013; 9: e1003657.
2. Kuiken T, Riteau B, Fouchier RA, Rimmelzwaan GF. Pathogenesis of influenza virus infections: the good, the bad and the ugly. Curr Opin Virol 2012; 2: 276-286.
3. Wu A, Su C, Wang D, Peng Y, Liu M, Hua S et al. Sequential reassortments underlie diverse influenza H7N9 genotypes in China. Cell Host Microbe 2013; 14: 446-452.
4. Gao R, Cao B, Hu Y, Feng Z, Wang D, Hu W et al. Human infection with a novel avian-origin influenza A (H7N9) virus. New Engl J Med 2013; 368: 1888-1897.
5. Short KR, Kroeze EJ, Fouchier RA, Kuiken T. Pathogenesis of influenza-induced acute respiratory distress syndrome. Lancet Infect Dis 2014; 14: 57-69.
6. Taubenberger JK, Morens DM. The pathology of influenza virus infections. Annu Rev Pathol 2008; 3: 499-522.
7. Rosen DG, Lopez AE, Anzalone ML, Wolf DA, Derrick SM, Florez LF et al. Postmortem findings in eight cases of influenza A/H1N1. Mod Pathol 2010; 23: 1449-1457.
8. Davison AM, Thomson D, Robson JS. Intravascular coagulation complicating influenza A virus infection. Br Med J 1973; 1: 654-655.
9. Watanabe T. Renal complications of seasonal and pandemic influenza A virus infections. Eur J Pediatr 2013; 172: 15-22.
10. Pang IK, Pillai PS, Iwasaki A. Efficient influenza A virus replication in the respiratory tract requires signals from TLR7 and RIG-I. Proc Natl Acad Sci USA 2013; 110: 13910-13915.
11. Gao R, Bhatnagar J, Blau DM, Greer P, Rollin DC, Denison AM et al. Cytokine and chemokine profiles in lung tissues from fatal cases of 2009 pandemic influenza A (H1N1): role of the host immune response in pathogenesis. Am J Pathol 2013; 183: 1258-1268.
12. McAuley JL, Tate MD, MacKenzie-Kludas CJ, Pinar A, Zeng W, Stutz A et al. Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. PLoS Pathog 2013; 9: e1003392.
13. Ichinohe T, Pang IK, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol 2010; 11: 404-410.
14. Lupfer C, Thomas PG, Anand PK, Vogel P, Milasta S, Martinez J et al. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection. Nat Immunol 2013; 14: 480-488.
15. Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nat Rev Immunol 2014; 14: 315-328.
16. Brandes M, Klauschen F, Kuchen S, Germain RN. A systems analysis identifies a feedforward inflammatory circuit leading to lethal influenza infection. Cell 2013; 154: 197-212.
17. Liu Q, Zhou YH, Yang ZQ. The cytokine storm of severe influenza and development of immunomodulatory therapy. Cell Mol Immunol 2016; 13: 3-10.
18. Armstrong SM, Darwish I, Lee WL. Endothelial activation and dysfunction in the pathogenesis of influenza A virus infection. Virulence 2013; 4: 537-542.
19. Antoniak S, Mackman N. Multiple roles of the coagulation protease cascade during virus infection. Blood 2014; 123: 2605-2613.
20. Le VB, Schneider JG, Boergeling Y, Berri F, Ducatez M, Guerin JL et al. Platelet activation and aggregation promote lung inflammation and influenza virus pathogenesis. Am J Respir Crit Care Med 2015; 191: 804-819.
21. Palta S, Saroa R, Palta A. Overview of the coagulation system. Indian J Anaesth 2014; 58: 515-523.
22. To KK, Song W, Lau SY, Que TL, Lung DC, Hung IF et al. Unique reassortant of influenza A(H7N9) virus associated with severe disease emerging in Hong Kong. J Infect 2014; 69: 60-68.
23. Chen E, Wang F, Lv H, Zhang Y, Ding H, Liu S et al. The first avian influenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report. Front Med 2013; 7: 333-344.
24. Chen Y, Liang W, Yang S, Wu N, Gao H, Sheng J et al. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet 2013; 381: 1916-1925.
25. Lu S, Li T, Xi X, Chen Q, Liu X, Zhang B et al. Prognosis of 18 H7N9 avian influenza patients in Shanghai. PLoS One 2014; 9: e88728.
26. Wiwanitkit V. Hemostatic disorders in bird flu infection. Blood Coagul Fibrinolysis 2008; 19: 5-6.
27. Claas EC, Osterhaus AD, van Beek R, De Jong JC, Rimmelzwaan GF, Senne DA et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 1998; 351: 472-477.
28. Harms PW, Schmidt LA, Smith LB, Newton DW, Pletneva MA, Walters LL et al. Autopsy findings in eight patients with fatal H1N1 influenza. Am J Clin Pathol 2010; 134: 27-35.
29. Soto-Abraham MV, Soriano-Rosas J, Diaz-Quinonez A, Silva-Pereyra J, Vazquez-Hernandez P, Torres-Lopez O et al. Pathological changes associated with the 2009 H1N1 virus. New Engl J Med 2009; 361: 2001-2003.
30. Gilbert CR, Vipul K, Baram M. Novel H1N1 influenza A viral infection complicated by alveolar hemorrhage. Respir Care 2010; 55: 623-625.
31. Mauad T, Hajjar LA, Callegari GD, da Silva LF, Schout D, Galas FR et al. Lung pathology in fatal novel human influenza A (H1N1) infection. Am J Respir Crit Care Med 2010; 181: 72-79.
32. Smeeth L, Cook C, Thomas S, Hall AJ, Hubbard R, Vallance P. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting. Lancet 2006; 367: 1075-1079.
33. Marsden PA. Inflammation and coagulation in the cardiovascular system: the contribution of influenza. Circ Res 2006; 99: 1152-1153.
34. Rothberg MB, Haessler SD, Brown RB. Complications of viral influenza. Am J Med 2008; 121: 258-264.
35. Kosugi N, Tsurutani Y, Isonishi A, Hori Y, Matsumoto M, Fujimura Y. Influenza A infection triggers thrombotic thrombocytopenic purpura by producing the anti-ADAMTS13 IgG inhibitor. Intern Med 2010; 49: 689-693.
36. Jonsson MK, Hammenfors D, Oppegaard O, Bruserud O, Kittang AO. A 35-year-old woman with influenza A-associated thrombotic thrombocytopenic purpura. Blood Coagul Fibrinolysis 2015; 26: 469-472.
37. Corrales-Medina VF, Madjid M, Musher DM. Role of acute infection in triggering acute coronary syndromes. Lancet Infect Dis 2010; 10: 83-92.
38. Ludwig A, Lucero-Obusan C, Schirmer P, Winston C, Holodniy M. Acute cardiac injury events p30 days after laboratory-confirmed influenza virus infection among U.S. veterans, 2010-2012. BMC Cardiovasc Disord 2015; 15: 109.
39. Barnes M, Heywood AE, Mahimbo A, Rahman B, Newall AT, Macintyre CR. Acute myocardial infarction and influenza: a metaanalysis of case-control studies. Heart 2015; 101: 1738-1747.
40. Warren-Gash C, Smeeth L, Hayward AC. Influenza as a trigger for acute myocardial infarction or death from cardiovascular disease: a systematic review. Lancet Infect Dis 2009; 9: 601-610.
41. Clar C, Oseni Z, Flowers N, Keshtkar-Jahromi M, Rees K. Influenza vaccines for preventing cardiovascular disease. Cochrane Database Syst Rev 2015; 5: CD005050.
42. Kwok CS, Aslam S, Kontopantelis E, Myint PK, Zaman MJ, Buchan I et al. Influenza, influenza-like symptoms and their association with cardiovascular risks: a systematic review and meta-analysis of observational studies. Int J Clin Pract 2015; 69: 928-937.
43. Rose JJ, Voora D, Cyr DD, Lucas JE, Zaas AK, Woods CW et al. Gene expression profiles link respiratory viral infection, platelet response to aspirin, and acute myocardial infarction. PLoS One 2015; 10: e0132259.
44. Lin HC, Chiu HF, Ho SC, Yang CY. Association of influenza vaccination and reduced risk of stroke hospitalization among the elderly: a population-based case-control study. Int J Environ Res Public Health 2014; 11: 3639-3649.
45. Granwehr B. ACP Journal Club. Review: influenza vaccination reduces cardiovascular events in adults. Ann Intern Med 2014; 160: JC2.
46. Kopel E, Klempfner R, Goldenberg I. Influenza vaccine and survival in acute heart failure. Eur J Heart Fail 2014; 16: 264-270.
47. Dobson J, Whitley RJ, Pocock S, Monto AS. Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials. Lancet 2015; 385: 1729-1737.
48. Keller TT, van der Sluijs KF, de Kruif MD, Gerdes VE, Meijers JC, Florquin S et al. Effects on coagulation and fibrinolysis induced by influenza in mice with a reduced capacity to generate activated protein C and a deficiency in plasminogen activator inhibitor type 1. Circ Res 2006; 99: 1261-1269.
49. Goeijenbier M, van Gorp EC, Van den Brand JM, Stittelaar K, Bakhtiari K, Roelofs JJ et al. Activation of coagulation and tissue fibrin deposition in experimental influenza in ferrets. BMC Microbiol 2014; 14: 134.
50. Herold S, Becker C, Ridge KM, Budinger GR. Influenza virus-induced lung injury: pathogenesis and implications for treatment. Eur Respir J 2015; 45: 1463-1478.
51. Akiyama R, Komori I, Hiramoto R, Isonishi A, Matsumoto M, Fujimura Y. H1N1 influenza (swine flu)-associated thrombotic microangiopathy with a markedly high plasma ratio of von Willebrand factor to ADAMTS13. Intern Med 2011; 50: 643-647.
52. Boilard E, Pare G, Rousseau M, Cloutier N, Dubuc I, Levesque T et al. Influenza virus H1N1 activates platelets through FcgammaRIIA signaling and thrombin generation. Blood 2014; 123: 2854-2863.
53. Teijaro JR, Walsh KB, Cahalan S, Fremgen DM, Roberts E, Scott F et al. Endothelial cells are central orchestrators of cytokine amplification during influenza virus infection. Cell 2011; 146: 980-991.
54. van Hinsbergh VW. Endothelium-role in regulation of coagulation and inflammation. Semin Immunopathol 2012; 34: 93-106.
55. Vallet B, Wiel E. Endothelial cell dysfunction and coagulation. Crit Care Med 2001; 29(7 Suppl): S36-S41.
56. Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 2007; 7: 803-815.
57. Pate M, Damarla V, Chi DS, Negi S, Krishnaswamy G. Endothelial cell biology: role in the inflammatory response. Adv Clin Chem 2010; 52: 109-130.
58. Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 2008; 133: 235-249.
59. Tsai SY, Segovia JA, Chang TH, Morris IR, Berton MT, Tessier PA et al. DAMP molecule S100A9 acts as a molecular pattern to enhance inflammation during influenza A virus infection: role of DDX21-TRIF-TLR4-MyD88 pathway. PLoS Pathog 2014; 10: e1003848.
60. Shibamiya A, Hersemeyer K, Schmidt Woll T, Sedding D, Daniel JM, Bauer S et al. A key role for Toll-like receptor-3 in disrupting the hemostasis balance on endothelial cells. Blood 2009; 113: 714-722.
61. Armstrong SM, Wang C, Tigdi J, Si X, Dumpit C, Charles S et al. Influenza infects lung microvascular endothelium leading to microvascular leak: role of apoptosis and claudin-5. PLoS One 2012; 7: e47323.
62. Wang S, Le TQ, Kurihara N, Chida J, Cisse Y, Yano M et al. Influenza virus-cytokine-protease cycle in the pathogenesis of vascular hyperpermeability in severe influenza. J Infect Dis 2010; 202: 991-1001.
63. Pinsky DJ, Naka Y, Liao H, Oz MC, Wagner DD, Mayadas TN et al. Hypoxia-induced exocytosis of endothelial cell Weibel-Palade bodies. A mechanism for rapid neutrophil recruitment after cardiac preservation. J Clin Invest 1996; 97: 493-500.
64. Walters KA, D'Agnillo F, Sheng ZM, Kindrachuk J, Schwartzman LM, Kuestner RE et al. 1918 pandemic influenza virus and Streptococcus pneumoniae co-infection results in activation of coagulation and widespread pulmonary thrombosis in mice and humans. J Pathol 2016; 238: 85-97.
65. Visseren FL, Bouwman JJ, Bouter KP, Diepersloot RJ, de Groot PH, Erkelens DW. Procoagulant activity of endothelial cells after infection with respiratory viruses. Thromb Haemost 2000; 84: 319-324.
66. Goeijenbier M, van Wissen M, van de Weg C, Jong E, Gerdes VE, Meijers JC et al. Review: viral infections and mechanisms of thrombosis and bleeding. J Med Virol 2012; 84: 1680-1696.
67. Teijaro JR, Walsh KB, Rice S, Rosen H, Oldstone MB. Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection. Proc Natl Acad Sci USA 2014; 111: 3799-3804.
68. Perrone LA, Plowden JK, Garcia-Sastre A, Katz JM, Tumpey TM. H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog 2008; 4: e1000115.
69. Sreeramkumar V, Adrover JM, Ballesteros I, Cuartero MI, Rossaint J, Bilbao I et al. Neutrophils scan for activated platelets to initiate inflammation. Science 2014; 346: 1234-1238.
70. Semple JW, Italiano JE Jr., Freedman J. Platelets and the immune continuum. Nat Rev Immunol 2011; 11: 264-274.
71. Tamagawa-Mineoka R. Important roles of platelets as immune cells in the skin. J Dermatol Sci 2015; 77: 93-101.
72. Vieira-de-Abreu A, Campbell RA, Weyrich AS, Zimmerman GA. Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum. Semin Immunopathol 2012; 34: 5-30.
73. Esmon CT, Xu J, Lupu F. Innate immunity and coagulation. J Thromb Haemost 2011; 9(Suppl 1): 182-188.
74. Stokes KY, Granger DN. Platelets: a critical link between inflammation and microvascular dysfunction. J Physiol 2012; 590: 1023-1034.
75. Klinger MH, Jelkmann W. Role of blood platelets in infection and inflammation. J Interferon Cytokine Res 2002; 22: 913-922.
76. Gawaz M, Langer H, May AE. Platelets in inflammation and atherogenesis. J Clin Invest 2005; 115: 3378-3384.
77. Morrell CN, Aggrey AA, Chapman LM, Modjeski KL. Emerging roles for platelets as immune and inflammatory cells. Blood 2014; 123: 2759-2767.
78. Rondina MT, Garraud O. Emerging evidence for platelets as immune and inflammatory effector cells. Front Immunol 2014; 5: 653.
79. Zarbock A, Polanowska-Grabowska RK, Ley K. Plateletneutrophil-interactions: linking hemostasis and inflammation. Blood Rev 2007; 21: 99-111.
80. Li J, Kim K, Barazia A, Tseng A, Cho J. Platelet-neutrophil interactions under thromboinflammatory conditions. Cell Mol Life Sci 2015; 72: 2627-2643.
81. Rossaint J, Zarbock A. Platelets in leucocyte recruitment and function. Cardiovasc Res 2015; 107: 386-395.
82. Siegel-Axel DI, Gawaz M. Platelets and endothelial cells. Semin Thromb Hemost 2007; 33: 128-135.
83. Henn V, Slupsky JR, Grafe M, Anagnostopoulos I, Forster R, Muller-Berghaus G et al. CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells. Nature 1998; 391: 591-594.
84. Danese S, Scaldaferri F, Papa A, Pola R, Gasbarrini A, Sgambato A et al. CD40L-positive platelets induce CD40L expression de novo in endothelial cells: adding a loop to microvascular inflammation. Arterioscler Thromb Vasc Biol 2004; 24: e162.
85. Kim JK, Jeon JS, Kim JW. Correlation between abnormal platelet count and respiratory viral infection in patients from Cheonan, Korea. J Clin Lab Anal 2014.
86. Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH et al. Clinical findings in 111 cases of influenza A (H7N9) virus infection. New Engl J Med 2013; 368: 2277-2285.
87. Lopez-Delgado JC, Rovira A, Esteve F, Rico N, Manez Mendiluce R, Ballus Noguera J et al. Thrombocytopenia as a mortality risk factor in acute respiratory failure in H1N1 influenza. Swiss Med Wkly 2013; 143: w13788.
88. Rondina MT, Brewster B, Grissom CK, Zimmerman GA, Kastendieck DH, Harris ES et al. In vivo platelet activation in critically ill patients with primary 2009 influenza A(H1N1). Chest 2012; 141: 1490-1495.
89. Khoufache K, Berri F, Nacken W, Vogel AB, Delenne M, Camerer E et al. PAR1 contributes to influenza A virus pathogenicity in mice. J Clin Invest 2013; 123: 206-214.
90. Sugiyama MG, Gamage A, Zyla R, Armstrong SM, Advani S, Advani A et al. Influenza virus infection induces platelet-endothelial adhesion which contributes to lung injury. J Virol 2015; 90: 1812-1823.
91. Mazur I, Wurzer WJ, Ehrhardt C, Pleschka S, Puthavathana P, Silberzahn T et al. Acetylsalicylic acid (ASA) blocks influenza virus propagation via its NF-kappaB-inhibiting activity. Cell Microbiol 2007; 9: 1683-1694.
92. Starko KM. Salicylates and pandemic influenza mortality, 1918-1919 pharmacology, pathology, and historic evidence. Clin Infect Dis 2009; 49: 1405-1410.
93. Eyers S, Weatherall M, Shirtcliffe P, Perrin K, Beasley R. The effect on mortality of antipyretics in the treatment of influenza infection: systematic review and meta-analysis. J R Soc Med 2010; 103: 403-411.
94. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557-560.
95. Yang Y, Sun R, Yang H, Zheng F, Gong F.-308 G 4 A of TNF-alpha gene promoter decreases the risk of multiple sclerosis: a meta-analysis. Mult Scler 2011; 17: 658-665.
96. Sunden Y, Park CH, Matsuda K, Anagawa A, Kimura T, Ochiai K et al. The effects of antipyretics on influenza virus encephalitis in mice and chicks. J Vet Med Sci 2003; 65: 1185-1188.
97. Davis LE, Green CL, Wallace JM. Influenza B virus model of Reye's syndrome in mice: the effect of aspirin. Ann Neurol 1985; 18: 556-559.
98. Crocker JF, Digout SC, Lee SH, Rozee KR, Renton K, Field CA et al. Effects of antipyretics on mortality due to influenza B virus in a mouse model of Reye's syndrome. Clin Invest Med 1998; 21: 192-202.
99. Bouwman JJ, Visseren FL, Bosch MC, Bouter KP, Diepersloot RJ. Procoagulant and inflammatory response of virus-infected monocytes. Eur J Clin Invest 2002; 32: 759-766.
100. Heemskerk JW, Bevers EM, Lindhout T. Platelet activation and blood coagulation. Thromb Haemost 2002; 88: 186-193.
101. Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol 2001; 167: 2887-2894.
102. Szaba FM, Smiley ST. Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo. Blood 2002; 99: 1053-1059.
103. Geisbert TW, Hensley LE, Jahrling PB, Larsen T, Geisbert JB, Paragas J et al. Treatment of Ebola virus infection with a recombinant inhibitor of factor VIIa/tissue factor: a study in rhesus monkeys. Lancet 2003; 362: 1953-1958.
104. Antoniak S, Owens AP 3rd, Baunacke M, Williams JC, Lee RD, Weithauser A et al. PAR-1 contributes to the innate immune response during viral infection. J Clin Invest 2013; 123: 1310-1322.
105. Khoufache K, LeBouder F, Morello E, Laurent F, Riffault S, Andrade-Gordon P et al. Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-gamma-dependent pathway. J Immunol 2009; 182: 7795-7802.
106. Nhu QM, Shirey K, Teijaro JR, Farber DL, Netzel-Arnett S, Antalis TM et al. Novel signaling interactions between proteinase-activated receptor 2 and Toll-like receptors in vitro and in vivo. Mucosal Immunol 2010; 3: 29-39.
107. Delvaeye M, Conway EM. Coagulation and innate immune responses: can we view them separately? Blood 2009; 114: 2367-2374.
108. Jackson CJ, Xue M. Activated protein C-an anticoagulant that does more than stop clots. Int J Biochem Cell Biol 2008; 40: 2692-2697.
109. Okajima K. Regulation of inflammatory responses by natural anticoagulants. Immunol Rev 2001; 184: 258-274.
110. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. New Engl J Med 2001; 344: 699-709.
111. Nick JA, Coldren CD, Geraci MW, Poch KR, Fouty BW, O'Brien J et al. Recombinant human activated protein C reduces human endotoxin-induced pulmonary inflammation via inhibition of neutrophil chemotaxis. Blood 2004; 104: 3878-3885.
112. Toltl LJ, Swystun LL, Pepler L, Liaw PC. Protective effects of activated protein C in sepsis. Thromb Haemost 2008; 100: 582-592.
113. Pestana D, de la Oliva P. Nebulized activated protein C in a paediatric patient with severe acute respiratory distress syndrome secondary to H1N1 influenza. Br J Anaesth 2011; 107: 818-819.
114. Schouten M, de Boer JD, van der Sluijs KF, Roelofs JJ, van't Veer C, Levi M et al. Impact of endogenous protein C on pulmonary coagulation and injury during lethal H1N1 influenza in mice. Am J Respir Cell Mol Biol 2011; 45: 789-794.
115. Schouten M, Sluijs KF, Gerlitz B, Grinnell BW, Roelofs JJ, Levi MM et al. Activated protein C ameliorates coagulopathy but does not influence outcome in lethal H1N1 influenza: a controlled laboratory study. Crit Care 2010; 14: R65.
116. Allen KS, Sawheny E, Kinasewitz GT. Anticoagulant modulation of inflammation in severe sepsis. World J Crit Care Med 2015; 4: 105-115.
117. Margetic S. Inflammation and haemostasis. Biochem Med 2012; 22: 49-62.
118. Ostrovsky L, Woodman RC, Payne D, Teoh D, Kubes P. Antithrombin III prevents and rapidly reverses leukocyte recruitment in ischemia/reperfusion. Circulation 1997; 96: 2302-2310.
119. Mizutani A, Okajima K, Uchiba M, Isobe H, Harada N, Mizutani S et al. Antithrombin reduces ischemia/reperfusion-induced renal injury in rats by inhibiting leukocyte activation through promotion of prostacyclin production. Blood 2003; 101: 3029-3036.
120. Congote LF. The C-terminal 26-residue peptide of serpin A1 is an inhibitor of HIV-1. Biochem Biophys Res Commun 2006; 343: 617-622.
121. Elmaleh DR, Brown NV, Geiben-Lynn R. Anti-viral activity of human antithrombin III. Int J Mol Med 2005; 16: 191-200.
122. Whitney JB, Asmal M, Geiben-Lynn R. Serpin induced antiviral activity of prostaglandin synthetase-2 against HIV-1 replication. PLoS One 2011; 6: e18589.
123. Quenelle DC, Hartman TL, Buckheit RW, Prichard MN, Lynn RG. Anti-HSV activity of serpin antithrombin III. Int Trends Immun 2014; 2: 87-92.
124. Asmal M, Seaman M, Lin W, Chung RT, Letvin NL, Geiben-Lynn R. Inhibition of HCV by the serpin antithrombin III. Virol J 2012; 9: 226.
125. Smee DF, Hurst BL, Day CW, Geiben-Lynn R. Influenza Virus H1N1 inhibition by serine protease inhibitor (serpin) antithrombin III. Int Trends Immun 2014; 2: 83-86.
126. Bahgat MM, Blazejewska P, Schughart K. Inhibition of lung serine proteases in mice: a potentially new approach to control influenza infection. Virol J 2011; 8: 27.
127. Peraramelli S, Rosing J, Hackeng TM. TFPI-dependent activities of protein S. Thromb Res 2012; 129(Suppl 2): S23-S26.
128. Wang Y, Chen J, Ling M, Lopez JA, Chung DW, Fu X. Hypochlorous acid generated by neutrophils inactivates ADAMTS13: an oxidative mechanism for regulating ADAMTS13 proteolytic activity during inflammation. J Biol Chem 2015; 290: 1422-1431.
129. Schwameis M, Schorgenhofer C, Assinger A, Steiner MM, Jilma B. VWF excess and ADAMTS13 deficiency: a unifying pathomechanism linking inflammation to thrombosis in DIC, malaria, and TTP. Thromb Haemost 2015; 113: 708-718.
130. Draxler DF, Medcalf RL. The fibrinolytic system-more than fibrinolysis? Transfus Med Rev 2015; 29: 102-109.
131. Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol 2005; 129: 307-321.
132. Godier A, Hunt BJ. Plasminogen receptors and their role in the pathogenesis of inflammatory, autoimmune and malignant disease. J Thromb Haemost 2013; 11: 26-34.
133. Syrovets T, Lunov O, Simmet T. Plasmin as a proinflammatory cell activator. J Leukoc Biol 2012; 92: 509-519.
134. LeBouder F, Morello E, Rimmelzwaan GF, Bosse F, Pechoux C, Delmas B et al. Annexin II incorporated into influenza virus particles supports virus replication by converting plasminogen into plasmin. J Virol 2008; 82: 6820-6828.
135. Goto H, Kawaoka Y. A novel mechanism for the acquisition of virulence by a human influenza A virus. Proc Natl Acad Sci USA 1998; 95: 10224-10228.
136. Goto H, Wells K, Takada A, Kawaoka Y. Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus. J Virol 2001; 75: 9297-9301.
137. Murakami M, Towatari T, Ohuchi M, Shiota M, Akao M, Okumura Y et al. Mini-plasmin found in the epithelial cells of bronchioles triggers infection by broad-spectrum influenza A viruses and Sendai virus. Eur J Biochem 2001; 268: 2847-2855.
138. Yao D, Kuwajima M, Kido H. Pathologic mechanisms of influenza encephalitis with an abnormal expression of inflammatory cytokines and accumulation of mini-plasmin. J Med Invest 2003; 50: 1-8.
139. Yao D, Chen Y, Kuwajima M, Shiota M, Kido H. Accumulation of mini-plasmin in the cerebral capillaries causes vascular invasion of the murine brain by a pneumotropic influenza A virus: implications for influenza-associated encephalopathy. Biol Chem 2004; 385: 487-492.
140. LeBouder F, Lina B, Rimmelzwaan GF, Riteau B. Plasminogen promotes influenza A virus replication through an annexin 2-dependent pathway in the absence of neuraminidase. J Gen Virol 2010; 91(Pt 11): 2753-2761.
141. Sun X, Tse LV, Ferguson AD, Whittaker GR. Modifications to the hemagglutinin cleavage site control the virulence of a neurotropic H1N1 influenza virus. J Virol 2010; 84: 8683-8690.
142. Tse LV, Marcano VC, Huang W, Pocwierz MS, Whittaker GR. Plasmin-mediated activation of pandemic H1N1 influenza virus hemagglutinin is independent of the viral neuraminidase. J Virol 2013; 87: 5161-5169.
143. Tse LV, Whittaker GR. Modification of the hemagglutinin cleavage site allows indirect activation of avian influenza virus H9N2 by bacterial staphylokinase. Virology 2015; 482: 1-8.
144. Berri F, Rimmelzwaan GF, Hanss M, Albina E, Foucault-Grunenwald ML, Le VB et al. Plasminogen controls inflammation and pathogenesis of influenza virus infections via fibrinolysis. PLoS Pathog 2013; 9: e1003229.
145. Yasar Yildiz S, Kuru P, Toksoy Oner E, Agirbasli M. Functional stability of plasminogen activator inhibitor-1. ScientificWorldJournal 2014; 2014: 858293.
146. Dittmann M, Hoffmann HH, Scull MA, Gilmore RH, Bell KL, Ciancanelli M et al. A serpin shapes the extracellular environment to prevent influenza A virus maturation. Cell 2015; 160: 631-643.
147. Visseren FL, Verkerk MS, Bouter KP, Diepersloot RJ, Erkelens DW. Interleukin-6 production by endothelial cells after infection with influenza virus and cytomegalovirus. J Lab Clin Med 1999; 134: 623-630.
148. Bhandary YP, Shetty SK, Marudamuthu AS, Midde KK, Ji HL, Shams H et al. Plasminogen activator inhibitor-1 in cigarette smoke exposure and influenza A virus infection-induced lung injury. PLoS One 2015; 10: e0123187.
149. Rynda-Apple A, Robinson KM, Alcorn JF. Influenza and bacterial superinfection: illuminating the immunologic mechanisms of disease. Infect Immun 2015; 83: 3764-3770.
150. McCullers JA. The co-pathogenesis of influenza viruses with bacteria in the lung. Nat Rev Microbiol 2014; 12: 252-262.
151. McCullers JA. Insights into the interaction between influenza virus and pneumococcus. Clin Microbiol Rev 2006; 19: 571-582.
152. Schuliga M. The inflammatory actions of coagulant and fibrinolytic proteases in disease. Mediators Inflamm 2015; 2015: 437695.
153. Zelaya H, Tsukida K, Chiba E, Marranzino G, Alvarez S, Kitazawa H et al. Immunobiotic lactobacilli reduce viral-associated pulmonary damage through the modulation of inflammation-coagulation interactions. Int Immunopharmacol 2014; 19: 161-173.
154. Zelaya H, Tada A, Vizoso-Pinto MG, Salva S, Kanmani P, Aguero G et al. Nasal priming with immunobiotic Lactobacillus rhamnosus modulates inflammation-coagulation interactions and reduces influenza virus-associated pulmonary damage. Inflamm Res 2015; 64: 589-602.
155. Zhirnov OP, Klenk HD, Wright PF. Aprotinin and similar protease inhibitors as drugs against influenza. Antiviral Res 2011; 92: 27-36.