Download PDF
Thromb Haemost 2009; 102(06): 1071-1079
DOI: 10.1160/TH09-03-0186
Theme Issue Article
Schattauer GmbH

Infection of the endothelium by members of the order Rickettsiales

Gustavo Valbuena
1   Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA
,
David H. Walker
2   Department of Pathology and Center for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston, Texas, USA
› Author AffiliationsFinancial support: NIH/NIAID U54 AI057156 (D.H. Walker, P.I.; G. Valbuena, Leader of Sub-Projects); NIH/NIAID 1R21AI069171 to G. Valbuena; NIH R01Al21242 to D.H. Walker.
Further Information

Publication History

Received: 20 March 2009

Accepted after minor revision: 26 July 2009

Publication Date:
28 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

The vascular endothelium is the main target of a limited number of infectious agents; Rickettsia, Ehrlichia ruminantium, and Orientia tsutsugamushi are among them. These arthropod-transmitted obligately-intracellular bacteria cause serious systemic diseases that are not infrequently lethal. In this review, we discuss the bacterial biology, vector biology, and clinical aspects of these conditions with particular emphasis on the interactions of these bacteria with the vascular endothelium and how it responds to intracellular infection. The study of these bacteria in relevant in vivo models is likely to offer new insights into the physiology of the endothelium that have not been revealed by other models.

Keywords

Rickettsia - Orientia tsutsugamushi - Ehrlichia ruminantium - endothelium - blood circulation
 

  • References

  • 1 Blanc G, Ogata H, Robert C. et al. Reductive genome evolution from the mother of Rickettsia . PLoS Genet 2007; 03: e14.
    CrossrefPubMedGoogle Scholar
  • 2 Darby AC, Cho NH, Fuxelius HH. et al. Intracellular pathogens go extreme: genome evolution in the Rickettsiales. Trends Genet 2007; 23: 511-520.
    CrossrefPubMedGoogle Scholar
  • 3 Fuxelius HH, Darby A, Min CK. et al. The genomic and metabolic diversity of Rickettsia . Res Microbiol 2007; 158: 745-753.
    CrossrefPubMedGoogle Scholar
  • 4 Walker DH, Bouyer DH. Rickettsia . In: Manual of Clinical Microbiology. 9th ed. American Society for Microbiology Press; 2007: 1036-1045.
    Google Scholar
  • 5 Walker DH, Ismail N. Emerging and re-emerging rickettsioses: endothelial cell infection and early disease events. Nat Rev Microbiol 2008; 06: 375-386.
    CrossrefPubMedGoogle Scholar
  • 6 Valbuena G, Walker DH. The endothelium as a target for infections. Annu Rev Pathol Mech Dis 2006; 01: 171-198.
    CrossrefPubMedGoogle Scholar
  • 7 Milazzo ML, Eyzaguirre EJ, Molina CP. et al. Maporal viral infection in the Syrian golden hamster: a model of hantavirus pulmonary syndrome. J Infect Dis 2002; 186: 1390-1395.
    CrossrefPubMedGoogle Scholar
  • 8 Zaki SR, Greer PW, Coffield LM. et al. Hantavirus pulmonary syndrome. Pathogenesis of an emerging infectious disease. Am J Pathol 1995; 146: 552-579.
    PubMedGoogle Scholar
  • 9 Boshoff C, Schulz TF, Kennedy MM. et al. Kaposi’s sarcoma-associated herpesvirus infects endothelial and spindle cells. Nat Med 1995; 01: 1274-1278.
    CrossrefPubMedGoogle Scholar
  • 10 Li JJ, Huang YQ, Cockerell CJ. et al. Localization of human herpes-like virus type 8 in vascular endothelial cells and perivascular spindle-shaped cells of Kaposi’s sarcoma lesions by in situ hybridization. Am J Pathol 1996; 148: 1741-1748.
    PubMedGoogle Scholar
  • 11 Moron CG, Popov VL, Feng HM. et al. Identification of the target cells of Orientia tsutsugamushi in human cases of scrub typhus. Mod Pathol 2001; 14: 752-759.
    CrossrefPubMedGoogle Scholar
  • 12 Prozesky L, Du Plessis JL. The pathology of heartwater. II. A study of the lung lesions in sheep and goats infected with the Ball3 strain of Cowdria ruminantium . Onderstepoort J Vet Res 1985; 52: 81-85.
    PubMedGoogle Scholar
  • 13 Bradford WD, Croker BP, Tisher CC. Kidney lesions in Rocky Mountain spotted fever: a light-, immunofluorescence-, and electron-microscopic study. Am J Pathol 1979; 97: 381-392.
    PubMedGoogle Scholar
  • 14 Kim J, Smith KJ, Naefie R. et al. Histopathologic features of and lymphoid populations in the skin of patients with the spotted fever group of rickettsiae: southern Africa. Int J Dermatol 2004; 43: 188-194.
    CrossrefPubMedGoogle Scholar
  • 15 Moe JB, Ruch GL, Kenyon RH. et al. Pathology of experimental Rocky Mountain spotted fever in rhesus monkeys. Vet Pathol 1976; 13: 69-77.
    CrossrefPubMedGoogle Scholar
  • 16 Moe JB, Mosher DF, Kenyon RH. et al. Functional and morphologic changes during experimental Rocky Mountain spotted fever in guinea pigs. Lab Invest 1976; 35: 235-245.
    PubMedGoogle Scholar
  • 17 Roggli VL, Keener S, Bradford WD. et al. Pulmonary pathology of Rocky Mountain spotted fever (RMSF) in children. Pediatr Pathol 1985; 04: 47-57.
    PubMedGoogle Scholar
  • 18 Mullen GR, O’Connor BM. Mites (Acari). In: Medical and Veterinary Entomology. First ed. Academic Press; 2002: 449-516.
    Google Scholar
  • 19 Lee JH, Cho NH, Kim SY. et al. Fibronectin facilitates the invasion of Orientia tsutsugamushi into host cells through interaction with a 56-kDa type-specific antigen. J Infect Dis 2008; 198: 250-257.
    CrossrefPubMedGoogle Scholar
  • 20 Chu H, Lee JH, Han SH. et al. Exploitation of the endocytic pathway by Orientia tsutsugamushi in nonprofessional phagocytes. Infect Immun 2006; 74: 4246-4253.
    CrossrefPubMedGoogle Scholar
  • 21 Gillespie JJ, Beier MS, Rahman MS. et al. Plasmids and rickettsial evolution: insight from Rickettsia felis . PLoS ONE 2007; 02: e266.
    CrossrefPubMedGoogle Scholar
  • 22 Gillespie JJ, Ammerman NC, Beier-Sexton M. et al. Louse- and flea-borne rickettsioses: biological and genomic analyses. Vet Res 2008; 40: 12.
    PubMedGoogle Scholar
  • 23 Gillespie JJ, Williams K, Shukla M. et al. Rickettsia phylogenomics: unwinding the intricacies of obligate intracellular life. PLoS ONE 2008; 03: e2018.
    CrossrefPubMedGoogle Scholar
  • 24 Heinzen RA, Hayes SF, Peacock MG. et al. Directional actin polymerization associated with spotted fever group Rickettsia infection of Vero cells. Infect Immun 1993; 61: 1926-1935.
    PubMedGoogle Scholar
  • 25 Heinzen RA, Grieshaber SS, Van Kirk LS. et al. Dynamics of actin-based movement by Rickettsia rickettsii in Vero cells. Infect Immun 1999; 67: 4201-4207.
    PubMedGoogle Scholar
  • 26 Van Kirk LS, Hayes SF, Heinzen RA. Ultrastructure of Rickettsia rickettsii actin tails and localization of cytoskeletal proteins. Infect Immun 2000; 68: 4706-4713.
    CrossrefPubMedGoogle Scholar
  • 27 Vishwanath S. Antigenic relationships among the rickettsiae of the spotted fever and typhus groups. FEMS Microbiol Lett 1991; 65: 341-344.
    PubMedGoogle Scholar
  • 28 Hackstadt T. The biology of rickettsiae. Infect Agents Dis 1996; 05: 127-143.
    PubMedGoogle Scholar
  • 29 Bozeman FM, Masiello SA, Williams MS. et al. Epidemic typhus rickettsiae isolated from flying squirrels. Nature 1975; 255: 545-547.
    CrossrefPubMedGoogle Scholar
  • 30 Duma RJ, Sonenshine DE, Bozeman FM. et al. Epidemic typhus in the United States associated with flying squirrels. JAMA 1981; 245: 2318-2323.
    CrossrefPubMedGoogle Scholar
  • 31 McDade JE, Shepard CC, Redus MA. et al. Evidence of Rickettsia prowazekii infections in the United States. Am J Trop Med Hyg 1980; 29: 277-284.
    CrossrefPubMedGoogle Scholar
  • 32 Sonenshine DE, Bozeman FM, Williams MS. et al. Epizootiology of epidemic typhus (Rickettsia prowazekii) in flying squirrels. Am J Trop Med Hyg 1978; 27: 339-349.
    CrossrefPubMedGoogle Scholar
  • 33 Medina-Sanchez A, Bouyer DH, Alcantara-Rodriguez V. et al. Detection of a typhus group Rickettsia in Amblyomma ticks in the state of Nuevo Leon, Mexico. Ann N Y Acad Sci 2005; 1063: 327-332.
    CrossrefPubMedGoogle Scholar
  • 34 Durden LA. Lice (Phthiraptera). In: Medical and Veterinary Entomology. First ed. Academic Press; 2002: 45-65.
    Google Scholar
  • 35 Traub R, Wisseman CL, Azad AF. The ecology of murine typhus-a critical review. Trop Dis Bull 1978; 75: 237-317.
    PubMedGoogle Scholar
  • 36 Azad AF. Relationship of vector biology and epidemiology of louse- and flea-borne rickettsioses. In: Biology of rickettsial diseases. First ed. CRC Press, Inc; 1988: 51-62.
    Google Scholar
  • 37 Gross L. How Charles Nicolle of the Pasteur Institute discovered that epidemic typhus is transmitted by lice: reminiscences from my years at the Pasteur Institute in Paris. Proc Natl Acad Sci U S A 1996; 93: 10539-10540.
    CrossrefPubMedGoogle Scholar
  • 38 Durden LA, Traub R. Fleas (Siphonaptera). In: Medical and Veterinary Entomology. First ed. Academic Press; 2002: 103-25.
    Google Scholar
  • 39 Sonenshine DE, Lane RS, Nicholson WL. Ticks (Ixodida). In: Medical and Veterinary Entomology. First ed. Academic Press; 2002: 517-58.
    Google Scholar
  • 40 Balashov YS. Bloodsucking ticks (Ixodidae). Vectors of disease of man and animals. First ed. Entomological Society of America; 1972
    Google Scholar
  • 41 Martinez JJ, Seveau S, Veiga E. et al. Ku70, a component of DNA-dependent protein kinase, is a mammalian receptor for Rickettsia conorii . Cell 2005; 123: 1013-1023.
    CrossrefPubMedGoogle Scholar
  • 42 Martinez JJ, Cossart P. Early signaling events involved in the entry of Rickettsia conorii into mammalian cells. J Cell Sci 2004; 117: 5097-5106.
    CrossrefPubMedGoogle Scholar
  • 43 Chan YG, Cardwell MM, Hermanas TM. et al. Rickettsial outer-membrane protein B (rOmpB) mediates bacterial invasion through Ku70 in an actin, c-Cbl, clathrin and caveolin 2-dependent manner. Cell Microbiol 2009; 11: 629-644.
    CrossrefPubMedGoogle Scholar
  • 44 Li H, Walker DH. rOmpA is a critical protein for the adhesion of Rickettsia rickettsii to host cells. Microb Pathog 1998; 24: 289-298.
    CrossrefPubMedGoogle Scholar
  • 45 Feng HM, Whitworth T, Popov V. et al. Effect of antibody on the Rickettsia-host cell interaction. Infect Immun 2004; 72: 3524-3530.
    CrossrefPubMedGoogle Scholar
  • 46 Renesto P, Dehoux P, Gouin E. et al. Identification and characterization of a phospholipase D-superfamily gene in rickettsiae. J Infect Dis 2003; 188: 1276-1283.
    CrossrefPubMedGoogle Scholar
  • 47 Radulovic S, Troyer JM, Beier MS. et al. Identification and molecular analysis of the gene encoding Rickettsia typhi hemolysin. Infect Immun 1999; 67: 6104-6108.
    PubMedGoogle Scholar
  • 48 Whitworth T, Popov VL, Yu XJ. et al. Expression of the Rickettsia prowazekii pld or tlyC gene in Salmonella enterica serovar Typhimurium mediates phagosomal escape. Infect Immun 2005; 73: 6668-6673.
    CrossrefPubMedGoogle Scholar
  • 49 Jardine JE, Vogel SW, van Kleef M. et al. Immunohistochemical identification of Cowdria ruminantium in formalin-fixed tissue sections from mice, sheep, cattle and goats. Onderstepoort J Vet Res 1995; 62: 277-280.
    PubMedGoogle Scholar
  • 50 Fatal cases of Rocky Mountain spotted fever in family clusters--three states, 2003. MMWR Morb Mortal Wkly Rep 2004; 53: 407-410.
    PubMedGoogle Scholar
  • 51 Paddock CD, Greer PW, Ferebee TL. et al. Hidden mortality attributable to Rocky Mountain spotted fever: immunohistochemical detection of fatal, serologically unconfirmed disease. J Infect Dis 1999; 179: 1469-1476.
    CrossrefPubMedGoogle Scholar
  • 52 Paddock CD, Holman RC, Krebs JW. et al. Assessing the magnitude of fatal Rocky Mountain spotted fever in the United States: comparison of two national data sources. Am J Trop Med Hyg 2002; 67: 349-354.
    CrossrefPubMedGoogle Scholar
  • 53 Lee N, Ip M, Wong B. et al. Risk factors associated with life-threatening rickettsial infections. Am J Trop Med Hyg 2008; 78: 973-978.
    PubMedGoogle Scholar
  • 54 Walker DH, Valbuena GA, Olano JP. Pathogenic mechanisms of diseases caused by Rickettsia . Ann N Y Acad Sci 2003; 990: 1-11.
    CrossrefPubMedGoogle Scholar
  • 55 George F, Brouqui P, Boffa MC. et al. 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: 2109-2116.
    PubMedGoogle Scholar
  • 56 La Scola B, Raoult D. Diagnosis of Mediterranean spotted fever by cultivation of Rickettsia conorii from blood and skin samples using the centrifugation-shell vial technique and by detection of R. conorii in circulating endothelial cells: a 6-year follow-up. J Clin Microbiol 1996; 34: 2722-2727.
    PubMedGoogle Scholar
  • 57 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: 263-272.
    CrossrefPubMedGoogle Scholar
  • 58 Walker DH, Lane TW. Rocky Mountain spotted fever: Clinical signs, symptoms, and pathophysiology. In: Biology of rickettsial diseases. First ed. CRC Press; 1988: 63-78.
    Google Scholar
  • 59 Woodward TE. Murine typhus fever: Its clinical and biologic similarity to epidemic typhus. In: Biology of rickettsial diseases. First ed. CRC Press, Inc; 1988: 79-92.
    Google Scholar
  • 60 Sexton D, Walker DH. Spotted fever group rickettsioses. In: Tropical infectious diseases. 2 ed. Elsevier; 2006: 539-547.
    Google Scholar
  • 61 Walker DH. Rickettsia rickettsii: as virulent as ever. Am J Trop Med Hyg 2002; 66: 448-449.
    CrossrefPubMedGoogle Scholar
  • 62 Raoult D, Woodward T, Dumler JS. The history of epidemic typhus. Infect Dis Clin North Am 2004; 18: 127-140.
    CrossrefPubMedGoogle Scholar
  • 63 Moe JB, Pedersen Jr CE. The impact of rickettsial diseases on military operations. Mil Med 1980; 145: 780-785.
    CrossrefPubMedGoogle Scholar
  • 64 Azad AF, Radulovic S. Pathogenic rickettsiae as bioterrorism agents. Ann N Y Acad Sci 2003; 990: 734-738.
    CrossrefPubMedGoogle Scholar
  • 65 Walker DH. Principles of the malicious use of infectious agents to create terror: reasons for concern for organisms of the genus Rickettsia . Ann N Y Acad Sci 2003; 990: 739-742.
    CrossrefPubMedGoogle Scholar
  • 66 Sonthayanon P, Chierakul W, Wuthiekanun V. et al. Association of high Orientia tsutsugamushi DNA loads with disease of greater severity in adults with scrub typhus. J Clin Microbiol 2009; 47: 430-434.
    CrossrefPubMedGoogle Scholar
  • 67 Paddock CD. Rickettsia parkeri as a paradigm for multiple causes of tick-borne spotted fever in the Western Hemisphere. Ann N Y Acad Sci 2005; 1063: 315-326.
    CrossrefPubMedGoogle Scholar
  • 68 Eremeeva ME, Klemt RM, Santucci-Domotor LA. et al. Genetic analysis of isolates of Rickettsia rickettsii that differ in virulence. Ann N Y Acad Sci 2003; 990: 717-722.
    CrossrefPubMedGoogle Scholar
  • 69 Ellison DW, Clark TR, Sturdevant DE. et al. Genomic comparison of virulent Rickettsia rickettsii Sheila Smith and avirulent Rickettsia rickettsii Iowa. Infect Immun 2008; 76: 542-550.
    CrossrefPubMedGoogle Scholar
  • 70 Schneider DS, Ayres JS. Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat Rev Immunol 2008; 08: 889-895.
    CrossrefPubMedGoogle Scholar
  • 71 Kaufmann SHE. Immunity to intracellular bacteria. In: Fundamental immunology. 5 ed. Lippincott Williams & Wilkins; 2003: 1229-61.
    Google Scholar
  • 72 Rydkina E, Sahni A, Silverman DJ. et al. Comparative analysis of host-cell signalling mechanisms activated in response to infection with Rickettsia conorii and Rickettsia typhi . J Med Microbiol 2007; 56: 896-906.
    CrossrefPubMedGoogle Scholar
  • 73 Damas JK, Davi G, Jensenius M. et al. Relative chemokine and adhesion molecule expression in Mediterranean spotted fever and African tick bite fever. J Infect 2009; 58: 68-75.
    CrossrefPubMedGoogle Scholar
  • 74 Hidalgo M, Sanchez R, Orejuela L. et al. Prevalence of antibodies against spotted fever group rickettsiae in a rural area of Colombia. Am J Trop Med Hyg 2007; 77: 378-380.
    PubMedGoogle Scholar
  • 75 Paddock CD, Finley RW, Wright CS. et al. Rickettsia parkeri rickettsiosis and its clinical distinction from Rocky Mountain spotted fever. Clin Infect Dis 2008; 47: 1188-1196.
    CrossrefPubMedGoogle Scholar
  • 76 Walker DH, Occhino C, Tringali GR. et al. Pathogenesis of rickettsial eschars: the tache noire of boutonneuse fever. Hum Pathol 1988; 19: 1449-1454.
    CrossrefPubMedGoogle Scholar
  • 77 Nachega JB, Bottieau E, Zech F. et al. Travel-acquired scrub typhus: emphasis on the differential diagnosis, treatment, and prevention strategies. J Travel Med 2007; 14: 352-355.
    CrossrefPubMedGoogle Scholar
  • 78 Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 2003; 16: 429-436.
    CrossrefPubMedGoogle Scholar
  • 79 Bechah Y, Capo C, Mege JL. et al. Epidemic typhus. Lancet Infect Dis 2008; 08: 417-426.
    CrossrefPubMedGoogle Scholar
  • 80 Chen LF, Sexton DJ. What’s new in Rocky Mountain spotted fever?. Infect Dis Clin North Am 2008; 22: 415-432.
    CrossrefPubMedGoogle Scholar
  • 81 Civen R, Ngo V. Murine typhus: an unrecognized suburban vectorborne disease. Clin Infect Dis 2008; 46: 913-918.
    CrossrefPubMedGoogle Scholar
  • 82 Walker DH, Paddock CD, Dumler JS. Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections. Med Clin North Am 2008; 92: 1345-1361.
    CrossrefPubMedGoogle Scholar
  • 83 Cines DB, Pollak ES, Buck CA. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-3561.
    PubMedGoogle Scholar
  • 84 Michiels C. Endothelial cell functions. J Cell Physiol 2003; 196: 430-443.
    CrossrefPubMedGoogle Scholar
  • 85 Danese S, Dejana E, Fiocchi C. Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J Immunol 2007; 178: 6017-6022.
    CrossrefPubMedGoogle Scholar
  • 86 Wagner DD, Frenette PS. The vessel wall and its interactions. Blood 2008; 111: 5271-5281.
    CrossrefPubMedGoogle Scholar
  • 87 Pober JS, Sessa WC. Evolving functions of endothelial cells in inflammation. Nat Rev Immunol 2007; 07: 803-815.
    CrossrefPubMedGoogle Scholar
  • 88 Rydkina E, Sahni A, Baggs RB. et al. Infection of human endothelial cells with spotted fever group rickettsiae stimulates cyclooxygenase 2 expression and release of vasoactive prostaglandins. Infect Immun 2006; 74: 5067-5074.
    CrossrefPubMedGoogle Scholar
  • 89 Woods ME, Wen G, Olano JP. Nitric oxide as a mediator of increased microvascular permeability during acute rickettsioses. Ann N Y Acad Sci 2005; 1063: 239-245.
    CrossrefPubMedGoogle Scholar
  • 90 Woods ME, Olano JP. Host defenses to Rickettsia rickettsii infection contribute to increased microvascular permeability in human cerebral endothelial cells. J Clin Immunol 2008; 28: 174-185.
    CrossrefPubMedGoogle Scholar
  • 91 Valbuena G, Walker DH. Changes in the adherens junctions of human endothelial cells infected with spotted fever group rickettsiae. Virchows Arch 2005; 446: 379-382.
    CrossrefPubMedGoogle Scholar
  • 92 Walker DH, Feng HM, Popov VL. Rickettsial phospholipase A2 as a pathogenic mechanism in a model of cell injury by typhus and spotted fever group rickettsiae. Am J Trop Med Hyg 2001; 65: 936-942.
    CrossrefPubMedGoogle Scholar
  • 93 Gouin E, Egile C, Dehoux P. et al. The RickA protein of Rickettsia conorii activates the Arp2/3 complex. Nature 2004; 427: 457-461.
    CrossrefPubMedGoogle Scholar
  • 94 Walker DH, Cain BG. The rickettsial plaque. Evidence for direct cytopathic effect of Rickettsia rickettsii . Lab Invest 1980; 43: 388-396.
    PubMedGoogle Scholar
  • 95 Teysseire N, Chiche-Portiche C, Raoult D. Intracellular movements of Rickettsia conorii and R. typhi based on actin polymerization. Res Microbiol 1992; 143: 821-829.
    CrossrefPubMedGoogle Scholar
  • 96 Silverman DJ. Rickettsia rickettsii-induced cellular injury of human vascular endothelium in vitro. Infect Immun 1984; 44: 545-553.
    PubMedGoogle Scholar
  • 97 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: 3110-3115.
    PubMedGoogle Scholar
  • 98 Devamanoharan PS, Santucci LA, Hong JE. et al. 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: 2619-2621.
    PubMedGoogle Scholar
  • 99 Hong JE, Santucci LA, Tian X. et al. Superoxide dismutase-dependent, catalase-sensitive peroxides in human endothelial cells infected by Rickettsia rickettsii . Infect Immun 1998; 66: 1293-1298.
    PubMedGoogle Scholar
  • 100 Santucci LA, Gutierrez PL, Silverman DJ. Rickettsia rickettsii induces superoxide radical and superoxide dismutase in human endothelial cells. Infect Immun 1992; 60: 5113-5118.
    PubMedGoogle Scholar
  • 101 Eremeeva ME, Silverman DJ. Effects of the antioxidant alpha-lipoic acid on human umbilical vein endothelial cells infected with Rickettsia rickettsii . Infect Immun 1998; 66: 2290-2299.
    PubMedGoogle Scholar
  • 102 Sahni SK, Rydkina E, Sahni A. et al. Potential roles for regulatory oxygenases in rickettsial pathogenesis. Ann N Y Acad Sci 2005; 1063: 207-214.
    CrossrefPubMedGoogle Scholar
  • 103 Sporn LA, Haidaris PJ, Shi RJ. et al. Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression. Blood 1994; 83: 1527-1534.
    PubMedGoogle Scholar
  • 104 Walker TS, Mellott GE. Rickettsial stimulation of endothelial platelet-activating factor synthesis. Infect Immun 1993; 61: 2024-2029.
    PubMedGoogle Scholar
  • 105 Teysseire N, Arnoux D, George F. et al. von Willebrand factor release and thrombomodulin and tissue factor expression in Rickettsia conorii-infected endothelial cells. Infect Immun 1992; 60: 4388-4393.
    PubMedGoogle Scholar
  • 106 Damas JK, Jensenius M, Ueland T. et al. Increased levels of soluble CD40L in African tick bite fever: possible involvement of TLRs in the pathogenic interaction between Rickettsia africae, endothelial cells, and platelets. J Immunol 2006; 177: 2699-2706.
    CrossrefPubMedGoogle Scholar
  • 107 Drancourt M, Alessi MC, Levy PY. et al. Secretion of tissue-type plasminogen activator and plasminogen activator inhibitor by Rickettsia conorii- and Rickettsia rickettsii-infected cultured endothelial cells. Infect Immun 1990; 58: 2459-2463.
    PubMedGoogle Scholar
  • 108 Sporn LA, Shi RJ, Lawrence SO. et al. Rickettsia rickettsii infection of cultured endothelial cells induces release of large von Willebrand factor multimers from Weibel-Palade bodies. Blood 1991; 78: 2595-2602.
    PubMedGoogle Scholar
  • 109 Schmaier AH, Srikanth S, Elghetany MT. et al. Haemostatic/fibrinolytic protein changes in C3H/HeN mice infected with Rickettsia conorii--a model for Rocky Mountain spotted fever. Thromb Haemost 2001; 86: 871-879.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 110 Sahni SK. Endothelial cell infection and hemostasis. Thromb Res 2007; 119: 531-549.
    CrossrefPubMedGoogle Scholar
  • 111 Kaplanski G, Teysseire N, Farnarier C. et al. IL-6 and IL-8 production from cultured human endothelial cells stimulated by infection with Rickettsia conorii via a cell-associated IL-1 alpha-dependent pathway. J Clin Invest 1995; 96: 2839-2844.
    CrossrefPubMedGoogle Scholar
  • 112 Sporn LA, Marder VJ. Interleukin-1 alpha production during Rickettsia rickettsii infection of cultured endothelial cells: potential role in autocrine cell stimulation. Infect Immun 1996; 64: 1609-1613.
    PubMedGoogle Scholar
  • 113 Dignat-George F, Teysseire N, Mutin M. et al. 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: 1142-1152.
    CrossrefPubMedGoogle Scholar
  • 114 Sporn LA, Lawrence SO, Silverman DJ. et al. E-selectin-dependent neutrophil adhesion to Rickettsia rickettsii-infected endothelial cells. Blood 1993; 81: 2406-2412.
    PubMedGoogle Scholar
  • 115 Walker TS, Brown JS, Hoover CS. et al. Endothelial prostaglandin secretion: effects of typhus rickettsiae. J Infect Dis 1990; 162: 1136-1144.
    CrossrefPubMedGoogle Scholar
  • 116 Bourdoulous S, Bensaid A, Martinez D. et al. Infection of bovine brain microvessel endothelial cells with Cowdria ruminantium elicits IL-1 beta, -6, and -8 mRNA production and expression of an unusual MHC class II DQ alpha transcript. J Immunol 1995; 154: 4032-4038.
    PubMedGoogle Scholar
  • 117 Walker DH, Popov VL, Wen J. et al. Rickettsia conorii infection of C3H/HeN mice. A model of endothelial-target rickettsiosis. Lab Invest 1994; 70: 358-368.
    PubMedGoogle Scholar
  • 118 Valbuena G, Bradford W, Walker DH. Expression analysis of the T-cell-targeting chemokines CXCL9 and CXCL10 in mice and humans with endothelial infections caused by rickettsiae of the spotted fever group. Am J Pathol 2003; 163: 1357-1369.
    CrossrefPubMedGoogle Scholar
  • 119 Valbuena G, Walker DH. Expression of CX3CL1 (fractalkine) in mice with endothelial-target rickettsial infection of the spotted-fever group. Virchows Arch 2004; 446: 21-27.
    PubMedGoogle Scholar
  • 120 Sahni SK, Van Antwerp DJ, Eremeeva ME. et al. Proteasome-independent activation of nuclear factor kappaB in cytoplasmic extracts from human endothelial cells by Rickettsia rickettsii . Infect Immun 1998; 66: 1827-1833.
    PubMedGoogle Scholar
  • 121 Sahni SK, Rydkina E, Joshi SG. et al. Interactions of Rickettsia rickettsii with endothelial nuclear factor-kappaB in a “cell-free” system. Ann N Y Acad Sci 2003; 990: 635-641.
    CrossrefPubMedGoogle Scholar
  • 122 Sporn LA, Sahni SK, Lerner NB. et al. Rickettsia rickettsii infection of cultured human endothelial cells induces NF-kappaB activation. Infect Immun 1997; 65: 2786-2791.
    PubMedGoogle Scholar
  • 123 Rydkina E, Silverman DJ, Sahni SK. Activation of p38 stress-activated protein kinase during Rickettsia rickettsii infection of human endothelial cells: role in the induction of chemokine response. Cell Microbiol 2005; 07: 1519-1530.
    CrossrefPubMedGoogle Scholar
  • 124 Clifton DR, Goss RA, Sahni SK. et al. NF-kappa B-dependent inhibition of apoptosis is essential for host cell survival during Rickettsia rickettsii infection. Proc Natl Acad Sci U S A 1998; 95: 4646-4651.
    CrossrefPubMedGoogle Scholar
  • 125 Yun JH, Koh YS, Lee KH. et al. Chemokine and cytokine production in susceptible C3H/HeN mice and resistant BALB/c mice during Orientia tsutsugamushi infection. Microbiol Immunol 2005; 49: 551-557.
    CrossrefPubMedGoogle Scholar
  • 126 Rao RM, Yang L, Garcia-Cardena G. et al. Endothelial-dependent mechanisms of leukocyte recruitment to the vascular wall. Circ Res 2007; 101: 234-247.
    CrossrefPubMedGoogle Scholar
  • 127 Bechah Y, Capo C, Raoult D. et al. Infection of endothelial cells with virulent Rickettsia prowazekii increases the transmigration of leukocytes. J Infect Dis 2008; 197: 142-147.
    CrossrefPubMedGoogle Scholar
  • 128 Walker DH, Olano JP, Feng HM. Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection. Infect Immun 2001; 69: 1841-1846.
    CrossrefPubMedGoogle Scholar
  • 129 Herrero-Herrero JI, Walker DH, Ruiz-Beltran R. Immunohistochemical evaluation of the cellular immune response to Rickettsia conorii in taches noires. J Infect Dis 1987; 155: 802-805.
    CrossrefPubMedGoogle Scholar
  • 130 Bagai R, Valujskikh A, Canaday DH. et al. Mouse endothelial cells cross-present lymphocyte-derived antigen on class I MHC via a TAP1- and proteasomedependent pathway. J Immunol 2005; 174: 7711-7715.
    CrossrefPubMedGoogle Scholar
  • 131 Choi J, Enis DR, Koh KP. et al. T lymphocyte-endothelial cell interactions. Annu Rev Immunol 2004; 22: 683-709.
    CrossrefPubMedGoogle Scholar
  • 132 Pober JS. Immunobiology of human vascular endothelium. Immunol Res 1999; 19: 225-232.
    CrossrefPubMedGoogle Scholar
  • 133 Epperson DE, Pober JS. Antigen-presenting function of human endothelial cells. Direct activation of resting CD8 T cells. J Immunol 1994; 153: 5402-5412.
    PubMedGoogle Scholar
  • 134 Savage CO, Brooks CJ, Harcourt GC. et al. Human vascular endothelial cells process and present autoantigen to human T cell lines. Int Immunol 1995; 07: 471-479.
    CrossrefPubMedGoogle Scholar
  • 135 Savinov AY, Wong FS, Stonebraker AC. et al. Presentation of antigen by endothelial cells and chemoattraction are required for homing of insulin-specific CD8+ T cells. J Exp Med 2003; 197: 643-656.
    CrossrefPubMedGoogle Scholar
  • 136 Marelli-Berg FM, James MJ, Dangerfield J. et al. Cognate recognition of the endothelium induces HYspecific CD8+ T-lymphocyte transendothelial migration (diapedesis) in vivo. Blood 2004; 103: 3111-3116.
    CrossrefPubMedGoogle Scholar
  • 137 Valujskikh A, Lantz O, Celli S. et al. Cross-primed CD8(+) T cells mediate graft rejection via a distinct effector pathway. Nat Immunol 2002; 03: 844-851.
    CrossrefPubMedGoogle Scholar
  • 138 Rothermel AL, Wang Y, Schechner J. et al. Endothelial cells present antigens in vivo. BMC Immunol 2004; 05: 5-15.
    CrossrefPubMedGoogle Scholar
  • 139 Smith ME, Thomas JA. Cellular expression of lymphocyte function associated antigens and the intercellular adhesion molecule-1 in normal tissue. J Clin Pathol 1990; 43: 893-900.
    CrossrefPubMedGoogle Scholar
  • 140 Jollow KC, Zimring JC, Sundstrom JB. et al. CD40 ligation induced phenotypic and functional expression of CD80 by human cardiac microvascular endothelial cells. Transplantation 1999; 68: 430-439.
    CrossrefPubMedGoogle Scholar
  • 141 Prat A, Biernacki K, Becher B. et al. B7 expression and antigen presentation by human brain endothelial cells: requirement for proinflammatory cytokines. J Neuropathol Exp Neurol 2000; 59: 129-136.
    CrossrefPubMedGoogle Scholar
  • 142 Omari KI, Dorovini-Zis K. Expression and function of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) in an in vitro model of the human bloodbrain barrier. J Neuroimmunol 2001; 113: 129-141.
    CrossrefPubMedGoogle Scholar
  • 143 Ma W, Pober JS. Human endothelial cells effectively costimulate cytokine production by, but not differentiation of, naive CD4+ T cells. J Immunol 1998; 161: 2158-2167.
    PubMedGoogle Scholar
  • 144 Karmann K, Hughes CC, Schechner J. et al. CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression. Proc Natl Acad Sci U S A 1995; 92: 4342-4346.
    CrossrefPubMedGoogle Scholar
  • 145 Omari KM, Dorovini-Zis K. CD40 expressed by human brain endothelial cells regulates CD4+ T cell adhesion to endothelium. J Neuroimmunol 2003; 134: 166-178.
    CrossrefPubMedGoogle Scholar
  • 146 Reul RM, Fang JC, Denton MD. et al. CD40 and CD40 ligand (CD154) are coexpressed on microvessels in vivo in human cardiac allograft rejection. Transplantation 1997; 64: 1765-1774.
    CrossrefPubMedGoogle Scholar
  • 147 Kunitomi A, Hori T, Imura A. et al. Vascular endothelial cells provide T cells with costimulatory signals via the OX40/gp34 system. J Leukoc Biol 2000; 68: 111-118.
    PubMedGoogle Scholar
  • 148 Khayyamian S, Hutloff A, Buchner K. et al. ICOSligand, expressed on human endothelial cells, costimulates Th1 and Th2 cytokine secretion by memory CD4+ T cells. Proc Natl Acad Sci U S A 2002; 99: 6198-6203.
    CrossrefPubMedGoogle Scholar
  • 149 Lozanoska-Ochser B, Klein NJ, Huang GC. et al. Expression of CD86 on human islet endothelial cells facilitates T cell adhesion and migration. J Immunol 2008; 181: 6109-6116.
    CrossrefPubMedGoogle Scholar
  • 150 Kreisel D, Krupnick AS, Gelman AE. et al. Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: an alternative mechanism of allorecognition. Nat Med 2002; 08: 233-239.
    CrossrefPubMedGoogle Scholar
  • 151 Kreisel D, Krupnick AS, Balsara KR. et al. Mouse vascular endothelium activates CD8+ T lymphocytes in a B7-dependent fashion. J Immunol 2002; 169: 6154-6161.
    CrossrefPubMedGoogle Scholar
  • 152 Krupnick AS, Gelman AE, Barchet W. et al. Murine vascular endothelium activates and induces the generation of allogeneic CD4+25+Foxp3+ regulatory T cells. J Immunol 2005; 175: 6265-6270.
    CrossrefPubMedGoogle Scholar
  • 153 Vachiery N, Trap I, Totte P. et al. Inhibition of MHC class I and class II cell surface expression on bovine endothelial cells upon infection with Cowdria ruminantium . Vet Immunol Immunopathol 1998; 61: 37-48.
    CrossrefPubMedGoogle Scholar
  • 154 Walker DH, Popov VL, Crocquet-Valdes PA. et al. Cytokine-induced, nitric oxide-dependent, intracellular antirickettsial activity of mouse endothelial cells. Lab Invest 1997; 76: 129-138.
    PubMedGoogle Scholar
  • 155 Feng HM, Walker DH. Mechanisms of intracellular killing of Rickettsia conorii in infected human endothelial cells, hepatocytes, and macrophages. Infect Immun 2000; 68: 6729-6736.
    CrossrefPubMedGoogle Scholar
  • 156 Mutunga M, Preston PM, Sumption KJ. Nitric oxide is produced by Cowdria ruminantium-infected bovine pulmonary endothelial cells in vitro and is stimulated by gamma interferon. Infect Immun 1998; 66: 2115-2121.
    PubMedGoogle Scholar
  • 157 Chapman AS, Bakken JS, Folk SM. et al. Diagnosis and management of tickborne rickettsial diseases: Rocky Mountain spotted fever, ehrlichioses, and anaplasmosis--United States: a practical guide for physicians and other health-care and public health professionals. MMWR Recomm Rep 2006; 55: 1-27.
    PubMedGoogle Scholar
  • 158 Hoyt JC, Ballering J, Numanami H. et al. Doxycycline modulates nitric oxide production in murine lung epithelial cells. J Immunol 2006; 176: 567-572.
    CrossrefPubMedGoogle Scholar
  • 159 Ribeiro JM. Blood-feeding arthropods: live syringes or invertebrate pharmacologists?. Infect Agents Dis 1995; 04: 143-152.
    PubMedGoogle Scholar
  • 160 Wikel SK. Host immunity to ticks. Annu Rev Entomol 1996; 41: 1-22.
    CrossrefPubMedGoogle Scholar
  • 161 Wikel SK, Bergman D. Tick-host immunology: Significant advances and challenging opportunities. Parasitol Today 1997; 13: 383-389.
    CrossrefPubMedGoogle Scholar
  • 162 Wikel SK. Tick modulation of host immunity: an important factor in pathogen transmission. Int J Parasitol 1999; 29: 851-859.
    CrossrefPubMedGoogle Scholar
  • 163 Brossard M, Wikel SK. Tick immunobiology. Parasitology 2008; 129 Suppl S161-S176.
    PubMedGoogle Scholar
  • 164 Tyson KR, Elkins C, de Silva AM. A novel mechanism of complement inhibition unmasked by a tick salivary protein that binds to properdin. J Immunol 2008; 180: 3964-3968.
    CrossrefPubMedGoogle Scholar
  • 165 Ribeiro JM, Francischetti IM. Role of arthropod saliva in blood feeding: sialome and post-sialome perspectives. Annu Rev Entomol 2003; 48: 73-88.
    CrossrefPubMedGoogle Scholar
  • 166 Steen NA, Barker SC, Alewood PF. Proteins in the saliva of the Ixodida (ticks): pharmacological features and biological significance. Toxicon 2006; 47: 1-20.
    CrossrefPubMedGoogle Scholar
  • 167 Maxwell SS, Stoklasek TA, Dash Y. et al. Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells. Ann Trop Med Parasitol 2005; 99: 661-672.
    CrossrefPubMedGoogle Scholar
  • 168 Francischetti IM, Mather TN, Ribeiro JM. Tick saliva is a potent inhibitor of endothelial cell proliferation and angiogenesis. Thromb Haemost 2005; 94: 167-174.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 169 Fukumoto S, Sakaguchi T, You M. et al. Tick troponin I-like molecule is a potent inhibitor for angiogenesis. Microvasc Res 2006; 71: 218-221.
    CrossrefPubMedGoogle Scholar
  • 170 Brown J, Reading SJ, Jones S. et al. Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: a comparison with the human bladder cancer derived epithelial cell line T24/83. Lab Invest 2000; 80: 37-45.
    CrossrefPubMedGoogle Scholar
  • 171 Zhang R, Yang H, Li M. et al. Acceleration of endothelial-like cell differentiation from CD14+ monocytes in vitro. Exp Hematol 2005; 33: 1554-1563.
    CrossrefPubMedGoogle Scholar
  • 172 Bailey AS, Willenbring H, Jiang S. et al. Myeloid lineage progenitors give rise to vascular endothelium. Proc Natl Acad Sci U S A 2006; 103: 13156-13161.
    CrossrefPubMedGoogle Scholar
  • 173 Chen H, Campbell RA, Chang Y. et al. Pleiotrophin produced by multiple myeloma induces transdifferentiation of monocytes into vascular endothelial cells: a novel mechanism of tumor-induced vasculogenesis. Blood 2009; 113: 1992-2002.
    CrossrefPubMedGoogle Scholar
  • 174 Wang L, Li L, Shojaei F. et al. Endothelial and hematopoietic cell fate of human embryonic stem cells originates from primitive endothelium with hemangioblastic properties. Immunity 2004; 21: 31-41.
    CrossrefPubMedGoogle Scholar
  • 175 Zovein AC, Hofmann JJ, Lynch M. et al. Fate tracing reveals the endothelial origin of hematopoietic stem cells. Cell Stem Cell 2008; 03: 625-636.
    CrossrefPubMedGoogle Scholar
  • 176 Durr E, Yu J, Krasinska KM. et al. Direct proteomic mapping of the lung microvascular endothelial cell surface in vivo and in cell culture. Nat Biotechnol 2004; 22: 985-992.
    CrossrefPubMedGoogle Scholar
  • 177 Amatschek S, Kriehuber E, Bauer W. et al. Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment. Blood 2007; 109: 4777-4785.
    CrossrefPubMedGoogle Scholar
  • 178 Calabria AR, Shusta EV. A genomic comparison of in vivo and in vitro brain microvascular endothelial cells. J Cereb Blood Flow Metab 2008; 28: 135-148.
    CrossrefPubMedGoogle Scholar
  • 179 Lacorre DA, Baekkevold ES, Garrido I. et al. Plasticity of endothelial cells: rapid dedifferentiation of freshly isolated venule endothelial cells outside the lymphoid tissue microenvironment. Blood 2004; 103: 4164-4172.
    CrossrefPubMedGoogle Scholar
  • 180 Roy S, Patel D, Khanna S. et al. Transcriptomewide analysis of blood vessels laser captured from human skin and chronic wound-edge tissue. Proc Natl Acad Sci U S A 2007; 104: 14472-14477.
    CrossrefPubMedGoogle Scholar
  • 181 Dai G, Kaazempur-Mofrad MR, Natarajan S. et al. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc Natl Acad Sci U S A 2004; 101: 14871-14876.
    CrossrefPubMedGoogle Scholar
  • 182 Gaucher C, Devaux C, Boura C. et al. In vitro impact of physiological shear stress on endothelial cells gene expression profile. Clin Hemorheol Microcirc 2007; 37: 99-107.
    PubMedGoogle Scholar
  • 183 Liu Y, Zhang Y, Schmelzer K. et al. The antiinflammatory effect of laminar flow: the role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase. Proc Natl Acad Sci U S A 2005; 102: 16747-16752.
    CrossrefPubMedGoogle Scholar
  • 184 Aird WC. Spatial and temporal dynamics of the endothelium. J Thromb Haemost 2005; 03: 1392-1406.
    CrossrefPubMedGoogle Scholar
  • 185 Davies PF. Endothelial transcriptome profiles in vivo in complex arterial flow fields. Ann Biomed Eng 2008; 36: 563-570.
    CrossrefPubMedGoogle Scholar
  • 186 Murphy TJ, Thurston G, Ezaki T. et al. Endothelial cell heterogeneity in venules of mouse airways induced by polarized inflammatory stimulus. Am J Pathol 1999; 155: 93-103.
    CrossrefPubMedGoogle Scholar
  • 187 St CB, Rago C, Velculescu V. et al. Genes expressed in human tumor endothelium. Science 2000; 289: 1197-1202.
    CrossrefPubMedGoogle Scholar
  • 188 Di FL, Totani L, Dovizio M. et al. Induction of prostacyclin by steady laminar shear stress suppresses tumor necrosis factor-alpha biosynthesis via heme oxygenase-1 in human endothelial cells. Circ Res 2009; 104: 506-513.
    CrossrefPubMedGoogle Scholar
  • 189 Gerzanich V, Woo SK, Vennekens R. et al. De novo expression of Trpm4 initiates secondary hemorrhage in spinal cord injury. Nat Med 2009; 15: 185-191.
    CrossrefPubMedGoogle Scholar