Download PDF
Thromb Haemost 2003; 89(01): 18-24
DOI: 10.1055/s-0037-1613538
Review Article
Schattauer GmbH

Interaction of pathogens with the endothelium

Stefan Hippenstiel
1   Charité, Department of Internal Medicine/Infectious Diseases, Humboldt University, Berlin, Germany
,
Norbert Suttorp
1   Charité, Department of Internal Medicine/Infectious Diseases, Humboldt University, Berlin, Germany
› Author Affiliations
Further Information

Publication History

Received 21 October 2002

Accepted 29 October 2002

Publication Date:
09 December 2017 (online)

    Permissions and Reprints

Summary

The endothelium lines the inner surface of the vessel wall establishing a multifunctional, semi-permeable cellular barrier at blood-tissue interface. The large total surface of the endothelium is exposed to pathogens, pathogen-derived products as well as to agents of the activated host defense during an inflammatory reaction. The endothelium is not only specifically targeted by important infective agents like Rickettsiae (1) or Bartonella (2), it is involved in virtually most, if not all, acute inflammatory responses. Pathogens attack the endothelium by a wide variety of strategies, as different as activation of preformed receptor-mediated pathways in the endothelium, release of pore-forming exotoxins or intracellular replication and chronic parasitism. These pathophysiological forces affect the endothelial phenotype, resulting in endothelial barrier dysfunction, increased leukocyte-endothelial interaction, mediator release, and procoagulant activity. Moreover, endothelial responses retroact on the invading pathogen as well as on the host defense resulting in a complex and dynamic interaction (Fig. 1). Endothelial activation contributes considerably to inflammation and resulting clinical characteristics. In this context the endothelium is not just a passive victim, it rather aggravates the ongoing struggle with the pathogen. In this review we focus on some important mechanisms of the cellular microbiology of endothelial infection by bacteria and viruses.

Keywords

Endothelium - infection - inflammation - bacteria - virus
 

  • References

  • 1 Valbuena G, Feng HM, Walker DH. Mechanisms of immunity against rickettsiae. New perspectives and opportunities offered by unusual intracellular parasites. Microbes Infect 2002; 4: 625-33.
    CrossrefPubMedGoogle Scholar
  • 2 Dehio C. Bartonella interactions with endothelial cells and erythrocytes. Trends Micro-biol 2001; 9: 279-85.
    CrossrefPubMedGoogle Scholar
  • 3 Sinha B, Francois PP, Nusse O, Foti M, Hartford OM, Vaudaux P, Foster TJ, Lew DP, Herrmann M, Krause KH. Fibronectin-binding protein acts as Staphylococcus aureus invasin via fibronectin bridging to integrin α5β1 . Cell Microbiol 1999; 1: 101-17.
    CrossrefPubMedGoogle Scholar
  • 4 Sinha B, Francois P, Que YA, Hussain M, Heilmann C, Moreillon P, Lew D, Krause KH, Peters G, Herrmann M. Heterologously expressed Staphylococcus aureus fibronectin-binding proteins are sufficient for invasion of host cells. Infect Immun 2000; 68: 6871-8.
    CrossrefPubMedGoogle Scholar
  • 5 Massey RC, Kantzanou MN, Fowler T, Day NP, Schofield K, Wann ER, Berendt AR, Hook M, Peacock SJ. Fibronectin-binding protein A of Staphylococcus aureus has multiple, substituting, binding regions that mediate adherence to fibronectin and invasion of endothelial cells. Cell Microbiol 2001; 3: 839-51.
    CrossrefPubMedGoogle Scholar
  • 6 Flock JI. Extracellular-matrix-binding proteins as targets for the prevention of Staphylococcus aureus infections. Mol Med Today 1999; 5: 532-37.
    CrossrefPubMedGoogle Scholar
  • 7 Chavakis T, Hussain M, Kanse SM, Peters G, Bretzel RG, Flock JI, Herrmann M, Preissner KT. Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes. Nat Med 2002; 8: 687-93.
    CrossrefPubMedGoogle Scholar
  • 8 Krüll M, Klucken AC, Wuppermann FN, Fuhrmann O, Magerl C, Seybold J, Hippenstiel S, Hegemann JH, Jantos CA, Suttorp N. Signal transduction pathways activated in endothelial cells following infection with Chlamydia pneumoniae . J Immunol 1999; 162: 4834-41.
    PubMedGoogle Scholar
  • 9 Fuhrmann O, Arvand M, Gohler A, Schmid M, Krüll M, Hippenstiel S, Seybold J, Dehio C, Suttorp N. Bartonella henselae induces NF-kappaB-dependent upregulation of adhesion molecules in cultured human endothelial cells: possible role of outer membrane proteins as pathogenic factors. Infect Immun 2001; 69: 5088-97.
    CrossrefPubMedGoogle Scholar
  • 10 Bhakdi S, Grimminger F, Suttorp N, Walmrath D, Seeger W. Proteinaceous bacterial toxins and pathogenesis of sepsis syndrome and septic shock: the unknown connection. Med Microbiol Immunol 1994; 183: 119-44.
    PubMedGoogle Scholar
  • 11 Karch H. The role of virulence factors in enterohemorrhagic Escherichia coli (EHEC)-associated hemolytic-uremic syndrome. Se-min Thromb Hemost 2001; 27: 207-13.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Zysk G, Schneider-Wald BK, Hwang JH, Bejo L, Kim KS, Mitchell TJ, Hakenbeck R, Heinz HP. Pneumolysin is the main inducer of cyto-toxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae . Infect Immun 2001; 69: 845-52.
    CrossrefPubMedGoogle Scholar
  • 13 Suttorp N, Hessz T, Seeger W, Wilke A, Koob R, Lutz F, Drenckhahn D. Bacterial exotoxins and endothelial permeability for water and albumin in vitro. Am J Physiol 1988; 255: C368-76.
    CrossrefPubMedGoogle Scholar
  • 14 Seeger W, Walter H, Neuhof H, Suttorp N, Bhakdi S. Escherichia coli hemolysin causes thromboxane-mediated hypertension and vascular leakage in rabbit lungs. Prog Clin Biol Res 1989; 308: 67-72.
    PubMedGoogle Scholar
  • 15 Mayer K, Temmesfeld-Wollbrück B, Fried-land A, Olschewski H, Reich M, Seeger W, Grimminger AF. Severe microcirculatory abnormalities elicited by E. coli hemolysin in the rabbit ileum mucosa. Am J Respir Crit Care Med 1999; 160: 1171-8.
    CrossrefPubMedGoogle Scholar
  • 16 Krüll M, Dold C, Hippenstiel S, Rosseau S, Lohmeyer J, Suttorp N. Escherichia coli hemolysin and Staphylococcus aureus alpha-toxin potently induce neutrophil adhesion to cultured human endothelial cells. J Immunol 1996; 157: 4133-40.
    PubMedGoogle Scholar
  • 17 Cornelis GR. The Yersinia Ysc-Yop ’Type III’ weaponry. Nat Rev Mol Cell Biol 2002; 3: 742-54.
    CrossrefPubMedGoogle Scholar
  • 18 Andor A, Trulzsch K, Essler M, Roggenkamp A, Wiedemann A, Heesemann J, Aepfelbacher M. YopE of Yersinia, a GAP for Rho GTPases, selectively modulates Rac-dependent actin structures in endothelial cells. Cell Microbiol 2001; 3: 301-10.
    CrossrefPubMedGoogle Scholar
  • 19 Molestina RE, Klein JB, Miller RD, Pierce WH, Ramirez JA, Summersgill JT. Proteomic analysis of differentially expressed Chlamydia pneumoniae genes during persistent infection of HEp-2 cells. Infect Immun 2002; 70: 2976-81.
    CrossrefPubMedGoogle Scholar
  • 20 Underhill DM, Ozinsky A. Toll-like receptors: key mediators of microbe detection. Curr Opin Immunol 2002; 14: 103-10.
    CrossrefPubMedGoogle Scholar
  • 21 Edfeldt K, Swedenborg J, Hansson GK, Yan ZQ. Expression of toll-like receptors in human atherosclerotic lesions: a possible pathway for plaque activation. Circulation 2002; 105: 1158-61.
    PubMedGoogle Scholar
  • 22 Triantafilou M, Triantafilou K. Lipopolysaccharide recognition: CD14, TLRs and the LPS-activation cluster. Trends Immunol 2002; 23: 301-4.
    CrossrefPubMedGoogle Scholar
  • 23 Bussolino F, Mitola S, Serini G, Barillari G, Ensoli B. Interactions between endothelial cells and HIV-1. Int J Biochem Cell Biol 2001; 33: 371-90.
    CrossrefPubMedGoogle Scholar
  • 24 Summersgill JT, Molestina RE, Miller RD, Ramirez JA. Interactions of Chlamydia pneumoniae with human endothelial cells. J Infect Dis 2000; 181: S479-82.
    CrossrefPubMedGoogle Scholar
  • 25 Cundell DR, Gerard NP, Gerard C, Idanpaan-Heikkila I, Tuomanen EI. Streptococcus pneumoniae anchor to activated human cells by the receptor for platelet-activating factor. Nature 1995; 377: 435-8.
    CrossrefPubMedGoogle Scholar
  • 26 Nassif X, Bourdoulous S, Eugene E, Couraud PO. How do extracellular pathogens cross the blood-brain barrier?. Trends Microbiol 2002; 10: 227-32.
    CrossrefPubMedGoogle Scholar
  • 27 Schnittler HJ, Feldmann H. Molecular pathogenesis of filovirus infections: role of macrophages and endothelial cells. Curr Top Micro-biol Immunol 1999; 235: 175-204.
    PubMedGoogle Scholar
  • 28 Poole LJ, Yu Y, Kim PS, Zheng QZ, Pevsner J, Hayward GS. Altered patterns of cellular gene expression in dermal microvascular endothelial cells infected with Kaposi’s sarcoma-associated herpesvirus. J Virol 2002; 76: 3395-420.
    CrossrefPubMedGoogle Scholar
  • 29 Steele-Mortimer O, Knodler LA, Finlay BB. Poisons, ruffles and rockets: bacterial pathogens and the host cell cytoskeleton. Traffic 2000; 1: 107-18.
    CrossrefPubMedGoogle Scholar
  • 30 Drevets DA. Listeria monocytogenes virulence factors that stimulate endothelial cells. Infect Immun 1998; 66: 232-38.
    PubMedGoogle Scholar
  • 31 Wolf K, Hackstadt T. Sphingomyelin trafficking in Chlamydia pneumoniae-infected cells. Cell Microbiol 2001; 3: 145-52.
    CrossrefPubMedGoogle Scholar
  • 32 Peters CJ, Zaki SR. Role of the endothelium in viral hemorrhagic fevers. Crit Care Med 2002; 30: S268-73.
    CrossrefPubMedGoogle Scholar
  • 33 De Martin R, Hoeth M, Hofer-Warbinek R, Schmid JA. The transcription factor NF-kappa B and the regulation of vascular cell function. Arterioscler Thromb Vasc Biol 2000; 20: E83-8.
    CrossrefPubMedGoogle Scholar
  • 34 Hack CE, Zeerleder S. The endothelium in sepsis: source of and a target for inflammation. Crit Care Med 2001; 29: S21-S7.
    CrossrefPubMedGoogle Scholar
  • 35 Granger DN, Kubes P. The microcirculation and inflammation: modulation of leukocyte-endothelial cell adhesion. J Leukoc Biol 1994; 55: 662-75.
    CrossrefPubMedGoogle Scholar
  • 36 Vanhoutte PM, Mombouli JV. Vascular endothelium: vasoactive mediators. Prog Cardiovasc Dis 1996; 39: 229-38.
    CrossrefPubMedGoogle Scholar
  • 37 Suttorp N, Fuhrmann M, Tannert-Otto S, Grimminger F, Bhadki S. Pore-forming bacterial toxins potently induce release of nitric oxide in porcine endothelial cells. J Exp Med 1993; 178: 337-41.
    CrossrefPubMedGoogle Scholar
  • 38 Wang P. Adrenomedullin in sepsis and septic shock. Shock 1998; 10: 383-4.
    CrossrefPubMedGoogle Scholar
  • 39 Shindo T, Kurihara H, Maemura K, Kurihara Y, Kuwaki T, Izumida T, Minamino N, Ju KH, Morita H, Ohhashi Y, Kumada M, Kangawa K, Nagai R, Yazaki Y. Hypotension and resistance to lipopolysaccharide-induced shock in transgenic mice overexpressing adrenomedullin in their vasculature. Circulation 2000; 101: 2309-16.
    CrossrefPubMedGoogle Scholar
  • 40 Hippenstiel S, Witzenrath M, Schmeck B, Hocke A, Krisp M, Krüll M, Seybold J, Seeger W, Rascher W, Schütte H, Suttorp N. Adrenomedullin reduces endothelial hyper-permeability. Circ Res 2002; 91: 618-25.
    CrossrefPubMedGoogle Scholar
  • 41 McEver RP. Adhesive interactions of leukocytes, platelets, and the vessel wall during hemostasis and inflammation. Thromb Haemost 2001; 86: 746-56.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Coughlin SR. Protease-activated receptors in vascular biology. Thromb Haemost 2001; 86: 298-307.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Patti JM, Allen BL, McGavin MJ, Höök M. MSCRAMM-mediated adherence of microorganisms to host tissues. Annu Rev Microbiol 1994; 48: 585-617.
    CrossrefPubMedGoogle Scholar
  • 44 O’Brien L, Kerrigan SW, Kaw G, Hogan M, Penades J, Litt D, Fitzgerald DJ, Foster TJ, Cox D. Multiple mechanisms for the activation of human platelet aggregation by Staphylococcus aureus: roles for the clumping factors ClfA and ClfB, the serine-aspartate repeat protein SdrE and protein A. Mol Microbiol 2002; 44: 1033-44.
    CrossrefPubMedGoogle Scholar
  • 45 Sullam PM, Bayer AS, Foss WM, Cheung AL. Diminished platelet binding in vitro by Staphylococcus aureus is associated with reduced virulence in a rabbit model of infective endocarditis. Infect Immun 1996; 64: 4915-21.
    PubMedGoogle Scholar
  • 46 Lahteenmaki K, Kuusela P, Korhonen TK. Bacterial plasminogen activators and receptors. FEMS Microbiol Rev 2001; 25: 531-52.
    CrossrefPubMedGoogle Scholar
  • 47 Stevens T, Garcia JG, Shasby DM, Bhattacharya J, Malik AB. Mechanisms regulating endothelial cell barrier function. Am J Physiol Lung Cell Mol Physiol 2000; 279: L419-22.
    CrossrefPubMedGoogle Scholar
  • 48 Ljungh A, Wadstrom T. Interactions of bacterial adhesins with the extracellular matrix. Adv Exp Med Biol 1996; 408: 129-40.
    PubMedGoogle Scholar
  • 49 Noll G. Pathogenesis of atherosclerosis: a possible relation to infection. Atherosclerosis 1998; 140: S3-9.
    CrossrefPubMedGoogle Scholar
  • 50 Isberg RR, Barnes P. Dancing with the host; flow-dependent bacterial adhesion. Cell 2002; 110: 1-4.
    CrossrefPubMedGoogle Scholar
  • 51 Huang SH, Triche T, Jong AY. Infectomics: genomics and proteomics of microbial infections. Funct Integr Genomics 2002; 1: 331-44.
    CrossrefPubMedGoogle Scholar