RSS-Feed abonnieren
DOI: 10.1055/s-0037-1614014
Procoagulant Activity of Endothelial Cells after Infection with Respiratory Viruses
The authors wish to thank Mrs. Mathea Verkerk for technical assistance, Dr. Peter Kreuz Wendedich von dem Borne for isolation of factor VII and X and Dr. Hence J. M. Verhage for technical advice on the tissue factor assay. This work was supported by a grant from the ‘Stichting Diabetes Research’, the Netherlands.Publikationsverlauf
Received
26. Juni 1997
Accepted after resubmission
29. Februar 2000
Publikationsdatum:
14. Dezember 2017 (online)
Summary
Influenza virus epidemics are associated with excess mortality due to cardiovascular diseases. There are several case reports of excessive coagulation during generalised influenza virus infection. In this study, we demonstrate the ability of respiratory viruses (influenza A, influenza B, parainfluenza-1, respiratory syncytial virus, adenovirus, cytomegalovirus) to infect lung fibroblasts and human umbilical vein endothelial cells in culture. All viral pathogens induced procoagulant activity in infected endothelial cells, as determined in a one-stage clotting assay, by causing an average 55% reduction in the clotting time. When factor VII deficient plasma was used clotting time was not reduced. The induction of procoagulant activity was associated with a 4- to 5-fold increase in the expression of tissue factor, as measured by the generation of factor Xa. Both experiments indicate that the procoagulant activity of endothelial cells in response to infection with respiratory viruses is caused by upregulation of the extrinsic pathway. Although both enveloped viruses and a non-enveloped virus (adenovirus) induced procoagulant activity in endothelial cells by stimulating tissue factor expression, the role of the viral envelope in the assembly of the prothrombinase complex remains uncertain.
We conclude that both enveloped and non-enveloped respiratory viruses are capable of infecting cultured human endothelial cells and causing a shift from anticoagulant to procoagulant activity associated with the induction of tissue factor expression.
-
References
- 1 Hendrix MGR, Dormans PHJ, Kitslaar P, Bosman F, Bruggeman CA. The presence of CMV nucleic acids in arterial walls of atherosclerotic and nonatherosclerotic patients. Am J Pathol 1989; 134: 1151-7.
- 2 Hendrix MGR, Salimans MMM, Boven CPAv, Bruggeman CA. High prevalence of latently present cytomegalovirus in arterial wall of patients suffering from grade III atherosclerosis. Am J Pathol 1990; 136: 23-8.
- 3 Adam E, Melnick JL, Probstfield JL, Petrie BL, Burek J, Bailey KR, McCollum CH, DeBakey ME. High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis. Lancet 1987; 02: 291-3.
- 4 Melnick JL, Hu C, Burek J, Adam E, DeBakey ME. Cytomegalovirus DNA in arterial walls of patients with atherosclerosis. J Med Virol 1994; 42: 170-4.
- 5 van Dam-Mieras MCE, Muller AD, van Hinsbergh VWM, Mullers WJHA, Bomans PHH, Bruggeman CA. The procoagulant response of cytomegalovirus infected endothelial cells. Thromb Haemost 1992; 68 (03) 364-70.
- 6 Etingin OR, Silverstein RL, Friedman HM, Hajjar DP. Viral activation of the coagulation cascade: molecular interactions at the surface of infected endothelial cells. Cell 1990; 61: 657-62.
- 7 Vercellotti GM. Proinflammatory and procoagulant effects of herpes simplex infection on human endothelium. Blood Cells 1990; 16: 209-16.
- 8 Mazure G, Grundy JE, Nygard G, Hudson M, Khan K, Srai K, Dhillon AP, Pounder RE, Wakefield AJ. Measles virus induction of human endothelial cell tissue factor procoagulant activity in vitro. J Gen Virol 1994; 75: 2863-71.
- 9 Span AHM, van Boven CPA, Bruggeman CA. The effect of cytomegalovirus infection on the adherence of polymorphonuclear leukocytes to endothelial cells. Eur J Clin Invest 1989; 19: 542-8.
- 10 Etingin OR, Silverstein RL, Hajjar DP. Identification of a monocyte receptor on herpesvirus-infected endothelial cells. Proc Natl Acad Sci USA 1991; 88: 7200-3.
- 11 Hajjar DP, Nicholson AC. Viral activation of coagulation: implications for thrombosis and atherosclerosis. Ann N Y Acad Sci 1997; 811: 155-65.
- 12 Tillet HE, Smith JWG, Gooch CD. Excess deaths attributable to influenza in England and Wales: age and dead and artificial course. Int J Epidemiol 1983; 12: 344-56.
- 13 Sprenger MJW, Diepersloot RJA, Beyer WEP, Masurel N. Influenza related excess mortality in The Netherlands. Lancet 1990; 336: 382.
- 14 Sprenger MJW, Naelten vanMAMG, Mulder PGH. Influenza mortality and excess deaths in the elderly, 1967-1982. Epidem Inf 1989; 103: 633-41.
- 15 Bainton D, Jones GR, Hole D. Influenza and ischaemic heart disease as a possible trigger for acute myocardial infarction?. Int J Epidem 1978; 07: 231-9.
- 16 Mattila KJ. Viral and bacterial infections in acute myocardial infarction. J Intern Med 1989; 225: 293-6.
- 17 Spodick DH, Flessas AP, Johnson MM. Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol 1984; 53: 481-2.
- 18 Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. Symptoms of chronic bronchitis and the risk of coronary disease. Lancet 1996; 348: 567-72.
- 19 Engblom E, Ekfors TO, Meurman OH, Toivuren A, Nikoskelainen J. Fatal influenza A myocarditis with isolation of virus from the myocardium. Acta Med Scand 1982; 213 (01) 75-8.
- 20 Witzleb W, Witzleb H, Mehllorn J, Sprossig M, Wutzler P. Demonstration of influenza virus A in human heart by semiquantitative virus assay and immunofluorescence. Acta Virol 1976; 20: 168.
- 21 Edelen JS, Bender TR, Chin TDY. Encephalopathy and pericarditis during an outbreak of influenza. Am J Epidemiol 1974; 100: 79-84.
- 22 Middleton RM, Szymanski MT. Severe myositis during recovery from influenza. Lancet 1970; 02: 533-5.
- 23 Kessler HA, Trenholme GM, Harris AA, Levin SL. Acute myopathy associated with influenza A/Texas/1/177 infection. JAMA 1980; 243: 461-2.
- 24 Tevada H. Studies on platelets and interaction with particular reference to the interaction of influenza virus with blood platelets. Acta Hematol Jap 1969; 32: 45-9.
- 25 Tevada H, Baldini M, Ebbe S, Madoff MA. Interaction of influenza virus with blood platelets. Blood 1966; 28: 213-6.
- 26 Barshtein IuA, Frolov AF, Persidskii IuV, Gavrilov SV. Characteristics of the action of the influenza virus on the microcirculatory vessels in an experiment. Mikrobiol Zh 1989; 51 (04) 44-50.
- 27 Bogomolov BP, Barinov VG, Dviatkin AV, Shvedova LP, Arkharova MN Frolova IN, Isaeva NP, Karelina LA. Hemostasis in influenza and acute respiratory viral infections in the middle-aged and elderly. Ter Arkh 1990; 62 (07) 98-102.
- 28 Anisimova IuN, Trushnikova GV. Infectious-toxic shock and disseminated intravascular coagulation in a pregnant woman with influenza. Arkh Patol 1994; 56 (03) 79-82.
- 29 Shcheglovitova ON, Antonov AS, Kabaeva NV, Orlova TG. Interferon production by primary culture of human endothelial cells. Biull Eksp Biol Med 1989; 108 (11) 580-3.
- 30 Colden-Stanfield M, Cramer EB, Gallin EK. Comparison of apical and basal surfaces of confluent endothelial cells: patch-clamp and viral studies. Am J Physiol 1992; 263 (03) C573-83.
- 31 Colden-Stanfield M, Ratcliffe D, Cramer EB, Gallin EK. Characterization of influenza virus-induced leukocyte adherence to human umbilical vein endothelial cell monolayers. J Immunol 1993; 151 (01) 310-21.
- 32 Colden-Stanfield M, Kalinich JF, Gallin EK. Ionizing radiation increases endothelial and epithelial cell production of influenza virus and leukocyte adherence. J Immunol 1994; 153 (11) 5222-9.
- 33 Jaffe EA, Nachman RL, Becker CG, Minick RC. Culture of human endothelial cells derived from umbilical veins. J Clin Invest 1973; 52: 2745-56.
- 34 Reed LJ, Muench J. A simple method of estimating fifty per cent endpoints. Am J Hyg 1938; 27: 493.
- 35 Pronk A, Groot de PhG, Hoynck van Papendrecht AAGM, Verbrugh HA, Leguit P, Vroonhoven van ThJMV, Sixma JJ. Thrombogenicity and procoagulant activity of human mesothelial cells. Arter Thromb 1992; 12: 1428-36.
- 36 Bajaj SP, Papaport SI, Brown SF. Isolation and characterisation of human factor VII. J Biol Chem 1981; 256: 253-9.
- 37 Miletich JP, Jackson CM, Majerus PW. Properties of the factor Xa binding site on human platelets. J Biol Chem 1978; 253: 6908-16.
- 38 Meijers JCM, Tijburg PNM, Bouma BN. Inhibition of human blood coagulation factor Xa by alpha-2-macroglobulin. Biochem 1987; 26: 5932-7.
- 39 Cotran RS. New roles for the endothelium in inflammation and immunity. Am J Pathol 1987; 129: 407-13.
- 40 Aridssino D, Merlini PA, Ariens R, Coppola R, Bramucci E, Mannucci PM. Tissue-factor antigen and activity in human coronary atherosclerotic plaques. Lancet 1997; 349: 769-71.
- 41 Homburg CH, de Haas M, von dem Borne AE, Verhoeven AJ, Reutelingsperger CP, Roos D. Human neutrophils lose their surface Fc gamma RIII and acquire Annexin V binding sites during apoptosis in vitro. Blood 1995; 85 (02) 532-40.
- 42 Key NS, Vercellotti GM, Winkelmann JC, Moldow CF, Goodman JL, Esmon NL, Esmon CT, Jacob HS. Infection of vascular endothelial cells with herpes simplex virus enhances tissue factor activity and reduces thrombomodulin expression. Proc Natl Acad Sci USA 1990; 87: 7095-9.
- 43 Key NS, Bach RR, Vercellotti GM, Moldow CF. Herpes simplex virus type I does not require productive infection to induce tissue factor in human umbilical vein endothelial cells. Lab Invest 1993; 68 (06) 645-51.
- 44 Pryzdial ELG, Wright JF. Prothrombinase assembly on an enveloped virus: evidence that the cytomegalovirus surface contains procoagulant phospholipid. Blood 1994; 84 (11) 3749-57.
- 45 Visser MR, Tracy PB, Vercellotti GM, Goodman JL, White JG, Jacob HS. Enhanced thrombin generation and platelet binding on herpes simplex virus-infected endothelium. Proc Natl Acad Sci USA 1988; 85: 8227-30.