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Thromb Haemost 2001; 86(03): 871-879
DOI: 10.1055/s-0037-1616145
DOI: 10.1055/s-0037-1616145
Review Articles
Hemostatic/Fibrinolytic Protein Changes in C3H/HeN Mice Infected with Rickettsia conorii
A Model for Rocky Mountain Spotted FeverAlvin H. Schmaier
1
Departments of Internal Medicine and Pathology
,
Sujata Srikanth
1
Departments of Internal Medicine and Pathology
,
Tarek M. Elghetany
2
Department of Pathology, The University of Texas Medical Branch, Galvestson, TX, USA
,
Daniel Normolle
3
Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI
,
Sumita Gokhale
2
Department of Pathology, The University of Texas Medical Branch, Galvestson, TX, USA
,
Hui-Min Feng
2
Department of Pathology, The University of Texas Medical Branch, Galvestson, TX, USA
,
David H. Walker
2
Department of Pathology, The University of Texas Medical Branch, Galvestson, TX, USA
› Author Affiliations
Further Information
Publication History
Received
28 December 2000
Accepted after revision
02 April 2001
Publication Date:
14 December 2017 (online)
Summary
Changes in plasma hemostatic and fibrinolytic proteins were determined during courses of a murine model of fatal and non-fatal Rocky Mountain spotted fever. C3H/HeN mice were infected with Rickettsia conorii and coagulation and histopathologic studies were performed at prescribed periods of time. A significant decrease in plasma factor VIII activity and rise in plasma factor V procoagulant activity correlated with a fatal infection. Factor VII levels were unchanged; factor XI levels dropped early in the course in the lethally infected animals, but returned to normal. Factor XII, high molecular weight kininogen, and prekallikrein levels were unchanged by the sublethal infection. Prekallikrein levels fell during the lethal infection. Antithrombin concentrations were decreased significantly in all animals, but plasma plasminogen levels did not change in either group of animals. Nonocclusive thrombi were microscopically observed rarely and only in animals surviving a sublethal infection. A fall in tissue plasminogen activator activity and a rise in plasminogen activator inhibitor activity highly correlated with a lethal outcome. Lethal infection with R. conorii is associated with primary endothelial cell injury resulting in decreased tissue plasminogen activator and increased plasminogen activator inhibitor.
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References
- 1 Wolbach SB. Studies on Rocky Mountain spotted fever. J Med Research 1919; 41: 1-70.
- 2 Walker DH, Crawford CG, Cain BG. Rickettsial infection of the pulmonary microcirculation: the basis for interstitial pneumonitis in Rocky Mountain spotted fever. Hum Pathol 1980; 11: 263-72.
- 3 Walker DH, Mattern WD. Acute renal failure in Rocky Mountain spotted fever. Arch Intern Med 1980; 139: 443-8.
- 4 Horney LF, Walker DH. Meningoencephalitis as a major manifestation of Rocky Mountain spotted fever. South Med J 1988; 81: 915-8.
- 5 Wolbach SB, Todd JL, Palfrey FW. Pathology of typhus in man. The Etiology and Pathology of Typhus . Cambridge, Mass.: The League of Red Cross Societies at the Harvard University Press; 152-222.
- 6 Walker DH, Feng H-M, Ladner S, Billings AN, Zaki SR, Wear DJ, High-tower B. Immunohistochemical diagnosis of typhus rickettsioses using an anti-lipopolysaccharide monoclonal antibody. Mod Pathol 1997; 10: 1038-42.
- 7 Walker DH, Gear JHS. Correlation of the distribution of Rickettsia conorii, microscopic lesions, and clinical features in South African tick bite fever. Am J Trop Med Hyg 1985; 34: 361-71.
- 8 Walker DH, Parks FM, Betz TG, Taylor JP, Muehlberger JW. Histopathology and immunohistologic demonstration of the distribution of Rickettsia typhi in fatal murine typhus. Am J Clin Pathol 1989; 91: 720-4.
- 9 Li H, Walker DH. Characterization of rickettsial attachment to host cells by flow cytometry. Infect Immun 1992; 60: 2030-5.
- 10 Li H, Walker DH. rOmpA is a critical protein for the adhesion of Rickettsia rickettsii to host cells. Microbial Pathogen 1998; 24: 289-98.
- 11 Walker TS. Rickettsial interactions with human endothelial cells in vitro: adherence and entry. Infect Immun 1984; 44: 205-10.
- 12 Sporn LA, Sahni SK, Lerner NB, Marder VJ, Silverman DJ, Turpin LC, Schwab AL. Rickettsia rickettsii infection in cultured human endothelial cells induces NK- B activation. Infect Immun 1997; 65: 2786-91.
- 13 Clifton DR, Goss RA, Sahni SK, van Antwerp D, Baggs RB, Marder VJ, Silverman DJ, Sporn LA. NK-κB-dependent inhibition of apoptosis is essential for host cell survival during Rickettsia rickettsii infection. Proc Natl Acad Sci USA 1998; 95: 4646-51.
- 14 Sahni SK, van Antwerp DJ, Eremeeva ME, Silverman DJ, Marder VJ, Sporn LA. Proteasome-independent activation of nuclear factor B in cytoplasmic extracts from human endothelial cells by Rickettsia rickettsii . Infect Immun 1998; 66: 1827-33.
- 15 Silverman DJ, Santucci LA. Potential for free radical-induced lipid peroxidation as a cause of endothelial cell injury in Rocky Mountain spotted fever. Infect Immun 1988; 56: 3110-5.
- 16 Silverman DJ, Santucci LA. A potential protective role for thiols against cell injury caused by Rickettsia rickettsii . Ann NY Acad Sci 1990; 590: 111-7.
- 17 Silverman DJ, Santucci LA, Sekeyova Z. Heparin protects human endothelial cells infected by Rickettsia rickettsii . Infect Immun 1991; 59: 4505-10.
- 18 Santucci LA, Gutierrez PL, Silverman DJ. Rickettsia rickettsii induces superoxide radical and superoxide dismutase in human endothelial cells. Infect Immun 1992; 60: 5113-8.
- 19 Devamanoharan PS, Santucci LA, Hong JE, Tian X, Silverman DJ. Infection of human endothelial cells by Rickettsia rickettsii causes a significant reduction in the levels of key enzymes involved in protection against oxidative injury. Infect Immun 1994; 62: 2619-21.
- 20 Eremeeva ME, Silverman DJ. Effects of the antioxidant α-lipoic acid on human umbilical vein endothelial cells infected with Rickettsia rickettsii . Infect Immun 1998; 66: 2290-9.
- 21 Walker DH, Firth WT, Ballard JG, Hegarty BC. Role of phospholipase-associated penetration mechanism in cell injury by Rickettsia rickettsii . Infect Immun 1983; 40: 840-2.
- 22 Silverman DJ, Santucci LA, Meyers N, Sekeyova Z. Penetration of host cells by Rickettsia rickettsii appears to be mediated by a phospholipase of rickettsial origin. Infect Immun 1992; 60: 2733-40.
- 23 Woodward TE. Rickettsial Diseases. Isselbacher KJ, Braunwald E, Wilson JD, Martin JB, Fauci AS, Kasper DL. eds. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 1994: 747-57.
- 24 Sporn LA, Haidaris PJ, Shi R-J, Nemerson Y, Silverman DJ, Marder VJ. Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression. Blood 1994; 83: 1527-34.
- 25 Rao AK, Schapira M, Clements ML, Niewiarowski S, Budzynski AZ, Schmaier AH, Harpel PC, Blackwelder WC, Scherrer JR, Sobel E, Colman RW. A prospective study of platelets and plasma proteolytic systems during the early stages of Rocky Mountain spotted fever. N Engl J Med 1988; 318: 1021-8.
- 26 Deep WD, Schriever HG, Turner W. Defibrination syndrome in Rocky Mountain spotted fever: a case report with heparin therapy. Va Med Mon 1969; 96: 92-5.
- 27 Trigg JW. Hypofibrinogenemia in Rocky Mountain spotted fever. Report of a case. N Engl J Med 1964; 270: 1042-4.
- 28 Kurnick JE, Malinow SH, Snyderman MC. Disseminated intravascular coagulation in Rocky Mountain spotted fever. South Med J 1974; 67: 623-5.
- 29 Davidson MG, Breitschwerdt EB, Walker DH, Levy MG, Carlson CS, Hardie EM, Grindem CA, Nasisse MP. Vascular permeability and coagulation during Rickettsia rickettsii infection in dogs. Am J Vet Res 1990; 51: 165-70.
- 30 Mosher DF, Fine DP, Moe JB, Kenyon RH, Ruch GL. Studies of the coagulation and complement systems during experimental Rocky Mountain spotted fever in rhesus monkeys. J Infect Dis 1977; 135: 985-9.
- 31 Vicente V, Alberca I, Ruiz R, Herrero I, Gonzalez R, Portugal J. Coagulation abnormalities in patients with Mediterranean spotted fever. J Infect Dis 1986; 153: 128-31.
- 32 Vicente V, Alegre A, Ruiz R, Herrero JI, Portugal J. Kinin-prekallikrein system in Mediterranean spotted fever (letter). J Infect Dis 1986; 154: 541.
- 33 Vicente V, Espana F, Tabernero D, Estelles A, Aznar J, Hendl S, Griffin JH. Evidence of activation of the protein C pathway during acute vascular damage induced by Mediterranean spotted fever. Blood 1991; 78: 416-22.
- 34 Vicente V, Estelles A, Moraleda JM, Espana F, Aznar EJ. Fibrinolytic changes during acute vascular damage induced by Mediterranean spotted fever. Fibrinolysis 1993; 7: 324-9.
- 35 George F, Brouqui P, Boffa M-C, Mutin M, Drancourt M, Brisson C, Raoult D, Sampol J. Demonstration of Rickettsia conorii-induced endothelial injury in vivo by measuring circulating endothelial cells, thrombomodulin, and von Willebrand factor in patients with Mediterranean spotted fever. Blood 1993; 82: 2109-16.
- 36 Davi G, Giammarresi C, Vigneri S, Ganci A, Ferri C, DiFrancesco L, Vitale G, Mansueto S. Demonstration of Rickettsia conorii-induced coagulative and platelet activation in vivo in patients with Mediterranean spotted fever. Thromb Haemost 1995; 74: 631-4.
- 37 Dignat-George F, Teysseire N, Mutin M, Bardin N, Lesaule G, Raoult D, Sampol J. Rickettsia conorii infection enhances vascular cell adhesion molecule-1- and intercellular adhesion molecule-1-dependent mononuclear cell adherence to endothelial cells. J Infect Dis 1997; 175: 1142-52.
- 38 Walker TS, Mellott GE. Rickettsial stimulation of endothelial platelet-activating factor synthesis. Infect Immun 1993; 61: 2024-9.
- 39 Teysseire N, Arnoux D, George F, Sampol J, Raoult D. von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells. Infect Immun 1992; 60: 4388-93.
- 40 Sporn LA, Shi R-J, Lawrence SO, Silverman DJ, Marder VJ. Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies. Blood 1991; 78: 2595-602.
- 41 Drancourt M, Alessi M-C, Levy P-Y, Juhan-Vague I, Raoult D. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by Rickettsia conorii- and Rickettsia rickettsii-infected cultured endothelial cells. Infect Immun 1990; 58: 2459-63.
- 42 Shi R-J, Simpson-Haidaris PJ, Marder VJ, Silverman DJ, Sporn LA. Increased expression of plasminogen activator inhibitor-1 in R. rickettsii-infected endothelial cells. Thromb Haemost 1996; 75: 600-6.
- 43 Moe JB, Mosher DF, Kenyon RH, White JD, Stookey JL, Bagley LR, Fine DP. Functional and morphologic changes during experimental rocky mountain spotted fever in guinea pigs. Lab Invest 1976; 35: 235-45.
- 44 Elghetany TM, Walker DH. Hemostatic changes in Rocky Mountain spotted fever and Mediterranean spotted fever. Am J Clin Pathol 1999; 112: 159-68.
- 45 Walker DH, Popov VL, Wen J, Feng H-M. Rickettsia conorii infection of C3H/HeN mice a model of endothelial-target rickettsiosis. Lab Invest 1994; 70: 358-68.
- 46 Feng H-M, Popov VL, Walker DH. Depletion of gamma interferon and tumor necrosis factor alpha in mice with Rickettsia conorii-infected endothelium: Impairment of rickettsicidal nitric oxide production resulting in fatal, overwhelming rickettsial disease. Infect Immun 1994; 62: 1952-60.
- 47 Feng H-M, Popov VL, Yuoh G, Walker DH. Role of T-lymphocyte subsets in immunity to spotted fever group rickettsiae. J Immunol 1997; 158: 5314-20.
- 48 Walker DH, Olano JP, Feng H-M. Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection. Infect Immun 2001; 69: 1841-6.
- 49 Schmaier AH, Dahl LD, Rozemuller AJM, Roos RAC, Wagner SL, Chung R, Van Nostrand WE. Protease nexin-2/amyloid β Protein Precursor. A tight-binding inhibitor of coagulation factor IXa. J Clin Invest 1993; 92: 2540-5.
- 50 DeLa Cadena R, Scott CF, Colman RW. Evaluation of a functional micro-assay for determination of plasma prekallikrein. J Lab Clin Med 1987; 109: 601-7.
- 51 Odegard OR, Lie M, Abildgaard U. Heparin cofactor activity measured with an amidolytic method. Thromb Res 1975; 6: 287-94.
- 52 Lijnen HR, Van Hoef B, Beelen V, Collen D. Characterization of the murine plasma fibrinolytic system. J Biochem 1994; 224: 863-71.
- 53 Shi RJ, Simpson-Haidaris PJ, Lerner NB, Marder VJ, Silverman DJ, Sporn LA. Transcriptional regulation of endothelial cell tissue factor expression during Rickettsia rickettsii infection: involvement of the transcriptional factor NF-kappaB. Infection & Immunity 1998; 66: 1070-5.
- 54 Shi R-J, Simpson-Haidaris PJ, Marder VJ, Silverman DJ, Sporn LA. Increased expression of plasminogen activator inhibitor-1 in Rickettsia rickettsii-infected endothelial cells. Thromb Haemost 1996; 75: 600-6.
- 55 Sporn LA, Marder VJ. Interleukin-1 production during Rickettsia rickettsii infection of cultured endothelial cells: potential role in autocrine cell stimulation. Infection and Immunity 1996; 64: 1609-13.
- 56 Patrassi GM, Dal Bo Zanon R, Boscaro M, Martinelli S, Girolami A. Further studies on the hypercoagulable state of patients with Cushing’s syndrome. Thromb Haemost 1985; 54: 518-20.
- 57 Annamalai AE, Stewart GJ, Hansel B, Memoli M, Chiu HC, Manuel DW, Doshi K, Colman RW. Expression of factor V on human umbilical vein endothelial cells is modulated by cell injury. Arteriosclerosis 1986; 6: 196-202.
- 58 Gailani D, Broze Jr GJ. Factor XI activation in a revised model of blood coagulation. Science 1991; 253: 909-12.
- 59 Baglia FA, Walsh PN. Thrombin-mediate feedback activation of factor XI on the activated platelet surface is preferred over contact activation by factor XIIa or factor XIa. J Biol Chem 2000; 275: 20514-9.
- 60 Chung DW, Fujikawa K, McMullen BA, Davie EW. Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats. Biochemistry 1986; 25: 2410-7.
- 61 Fisher CA, Schmaier AH, Addonizio VP, Colman RW. Assay of prekallikrein in human plasma: comparison of amidolytic, esterolytic, coagulation, and immunochemical assays. Blood 1982; 59: 963-70.