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Thromb Haemost 2007; 98(04): 823-830
DOI: 10.1160/TH06-11-0665
Wound Healing and Inflammation/Infection
Schattauer GmbH

Haemophilus somnus activation of brain endothelial cells: Potential role for local cytokine production and thrombosis in central nervous system (CNS) infection

Erica Behling-Kelly
1   Comparative Biomedical Sciences Graduate Program, University of Wisconsin, Madison, Wisconsin, USA
,
Kwang S. Kim
2   Johns Hopkins, Baltimore, Maryland, USA
,
Charles J. Czuprynski
1   Comparative Biomedical Sciences Graduate Program, University of Wisconsin, Madison, Wisconsin, USA
› Author AffiliationsFinancial support: This work was supported by US Public Health Service Grant 1 K08A1057989 from the National Institute of Allergy and Infectious Diseases (to E. Behling-Kelly); by the National Research Initiative Competitive Grants 2005–01694 and 2000–02304 from the USDA Cooperative State Research, Education and Extension Service; and by the Wisconsin Agricultural Experimental Station Hatch funds (Project 03094).
Further Information

Publication History

Received 25 November 2007

Accepted after resubmission 26 June 2007

Publication Date:
01 December 2017 (online)

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Summary

Thrombotic meningoencephalitis (TME) is a neurological condition in cattle characterized by fibrinopurulent meningitis with hemorrhage, abscess formation and thrombotic vasculitis throughout the central nervous system. The etiologic agent of TME is Haemophilus somnus, a gram-negative pleomorphic coccobacillus. Although the pathogenesis of TME is not well understood, the propensity of H. somnus to cause vasculitis and intravascular thrombosis suggests a critical role for the interactions between the bacteria and endothelial cells in inciting the disease. The goal of this study was to determine if H. somnus elicits an inflammatory and procoagulative response in bovine brain micro- vascular endothelial cells (BBEC) in vitro. We demonstrate that BBEC exposed to H. somnus secrete significant levels of the proinflammatory and procoagulative cytokines TNF-α and IL-1β. BBEC treated with H. somnus also display increased levels of IL-6 mRNA,another cytokine associated with coagulopathy in vivo. H. somnus-treated BBEC exhibited increased procoagulant activity and tissue factor expression and activity,along with a decreased ability to activate protein C and decreased expression of thrombomodulin mRNA. These changes would be expected to promote thrombus formation in vessels of the CNS, and potentially contribute to the pathogenesis of TME.

Keywords

Endothelial - infection - brain - thrombosis - Haemophilus
 

  • References

  • 1 Janzen FW. The Haemophilus somnus disease complex (hemophilosis): a review.. Can Vet J 1989; 30: 816-822.
    PubMedGoogle Scholar
  • 2 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
  • 3 Esmon CT. The interactions between inflammation and coagulation.. Br J Haematol 2005; 131: 417-430.
    CrossrefPubMedGoogle Scholar
  • 4 Myers DD, Wakefield TW. Inflammation-dependent thrombosis.. Front Biosci 2005; 10: 2750-2757.
    CrossrefPubMedGoogle Scholar
  • 5 Strukova S. Blood coagulation-dependent inflammation. Coagulation-dependent inflammation and inflammation- dependent thrombosis.. Front Biosci 2006; 11: 59-80.
    CrossrefPubMedGoogle Scholar
  • 6 Schnittler HJ, Preissner KT. Vascular endothelium and infectious diseases: trick and treat.. Thromb Haemost 2005; 94: 238-239.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Bielaszewska M, Karch H. Consequences of enterohaemorrhagic Escherichia coli infection for the vascular endothelium.. Thromb Haemost 2005; 94: 312-318.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Stins MF, Prasadarao NV, Zhou J. et al. Bovine brain microvascular endothelial cells transfected with SV40-large T antigen: development of an immortalized cell line to study pathophysiology of CNS disease.. In Vitro Cell Dev Biol Anim 1997; 33: 243-247.
    CrossrefPubMedGoogle Scholar
  • 9 Hezi-Yamit A, Wong PW, Bien-Ly N. et al. Synergistic induction of tissue factor by coagulation factor Xa and TNF: evidence for involvement of negative regulatory signaling cascades.. Proc Natl Acad Sci USA 2005; 102: 12077-12082.
    CrossrefPubMedGoogle Scholar
  • 10 Esmon CT. The impact of the inflammatory response on coagulation.. Thromb Res 2004; 114: 321-327.
    CrossrefPubMedGoogle Scholar
  • 11 Lopes-Bezerra LM, Filler SG. Endothelial cells, tissue factor and infectious diseases.. Braz J Med Biol Res 2003; 36: 987-991.
    CrossrefPubMedGoogle Scholar
  • 12 Shebuski RJ, Kilgore KS. Role of inflammatory mediators in thrombogenesis.. J Pharmacol Exp Ther 2002; 300: 729-735.
    CrossrefPubMedGoogle Scholar
  • 13 Bach RR. Tissue factor encryption.. Arterioscler Thromb Vasc Biol 2006; 26: 456-461.
    PubMedGoogle Scholar
  • 14 Esmon CT. Protein C anticoagulant pathway and its role in controlling microvascular thrombosis and inflammation.. Crit Care Med 2001; 29: S48-51 discussion 51–52.
    CrossrefPubMedGoogle Scholar
  • 15 Pathan N, Faust SN, Levin M. Pathophysiology of meningococcal meningitis and septicaemia.. Arch Dis Child 2003; 88: 601-607.
    CrossrefPubMedGoogle Scholar
  • 16 Brandtzaeg P, Bjerre A, Ovstebo R. et al. Neisseria meningitidis lipopolysaccharides in human pathology.. J Endotoxin Res 2001; 7: 401-420.
    PubMedGoogle Scholar
  • 17 Heyderman RS, Klein NJ, Daramola OA. et al. Induction of human endothelial tissue factor expression by Neisseria meningitidis: the influence of bacterial killing and adherence to the endothelium.. Microb Pathog 1997; 22: 265-274.
    CrossrefPubMedGoogle Scholar
  • 18 Mirlashari MR, Hoiby EA, Holst J. et al. Outer membrane vesicles from Neisseria meningitidis: effects on tissue factor and plasminogen activator inhibitor- 2 production in human monocytes.. Thromb Res 2001; 102: 375-380.
    CrossrefPubMedGoogle Scholar
  • 19 Czuprynski CJ, Leite F, Sylte M. et al. Complexities of the pathogenesis of Mannheimia haemolytica and Haemophilus somnus infections: challenges and potential opportunities for prevention?. Anim Health Res Rev 2004; 5: 277-282.
    CrossrefPubMedGoogle Scholar
  • 20 Sylte MJ, Corbeil LB, Inzana TJ. et al. Haemophilus somnus induces apoptosis in bovine endothelial cells in vitro.. Infect Immun 2001; 69: 1650-1660.
    CrossrefPubMedGoogle Scholar
  • 21 Bombeli T, Karsan A, Tait JF. et al. Apoptotic vascular endothelial cells become procoagulant.. Blood 1997; 89: 2429-2442.
    PubMedGoogle Scholar
  • 22 Kuckleburg CJ, Elswaifi SF, Inzana TJ. et al. Expression of phosphorylcholine by Histophilus somni induces bovine platelet aggregation.. Infect Immun 2007; 75: 1045-1049.
    CrossrefPubMedGoogle Scholar
  • 23 Thompson KG, Little PB. Effect of Haemophilus somnus on bovine endothelial cell in organ culture.. Am J Vet Res 1981; 42: 748-754.
    PubMedGoogle Scholar
  • 24 Behling-Kelly E, McClenahan O, Kim KS. et al. Viable Haemophilus somnus induces myosin light-chain kinase-dependent decrease in brain endothelial monolayer resistance.. Infect Immun 2007; 75: 4572-4581.
    CrossrefPubMedGoogle Scholar
  • 25 Behling-Kelly E, Vonderheid H, Kim KS. et al. Roles of cellular activation and sulfated glycans in Haemophilus somnus adherence to bovine brain microvascular endothelial cells.. Infect Immun 2006; 74: 5311-5318.
    CrossrefPubMedGoogle Scholar
  • 26 Taha MK. Neisseria meningitidis induces the expression of the TNF-alpha gene in endothelial cells.. Cytokine 2000; 12: 21-25.
    CrossrefPubMedGoogle Scholar
  • 27 Verma S, Nakaoke R, Dohgu S. et al. Release of cytokines by brain endothelial cells: A polarized response to lipopolysaccharide.. Brain Behav Immun 2006; 20: 449-455.
    CrossrefPubMedGoogle Scholar
  • 28 Liu Y, Pelekanakis K, Woolkalis MJ. Thrombin and tumor necrosis factor alpha synergistically stimulate tissue factor expression in human endothelial cells: Regulation through c-Fos and c-Jun.. J Biol Chem 2004; 279: 36142-36147.
    CrossrefPubMedGoogle Scholar
  • 29 Nawroth PP, Handley DA, Esmon CT. et al. Interleukin 1 induces endothelial cell procoagulant while suppressing cell-surface anticoagulant activity.. Proc Natl Acad Sci USA 1986; 83: 3460-3464.
    CrossrefPubMedGoogle Scholar
  • 30 Stern DM, Bank I, Nawroth PP. et al. Self-regulation of procoagulant events on the endothelial cell surface.. J Exp Med 1985; 162: 1223-1235.
    CrossrefPubMedGoogle Scholar
  • 31 Emerson Jr., TE, Lindsey DC, Jesmok GJ. et al. Efficacy of monoclonal antibody against tumor necrosis factor alpha in an endotoxemic baboon model.. Circ Shock 1992; 38: 75-84.
    PubMedGoogle Scholar
  • 32 Szotowski B, Antoniak S, Poller W. et al. Procoagulant soluble tissue factor is released from endothelial cells in response to inflammatory cytokines.. Circ Res 2005; 96: 1233-1239.
    CrossrefPubMedGoogle Scholar
  • 33 Wada H, Tanigawa M, Wakita Y. et al. Increased plasma level of interleukin-6 in disseminated intravascular coagulation.. Blood Coagul Fibrinolysis 1993; 4: 583-590.
    CrossrefPubMedGoogle Scholar
  • 34 van der Poll T, Levi M, Hack CE. et al. Elimination of interleukin 6 attenuates coagulation activation in experimental endotoxemia in chimpanzees.. J Exp Med 1994; 179: 1253-1259.
    CrossrefPubMedGoogle Scholar
  • 35 Derhaschnig U, Bergmair D, Marsik C. et al. Effect of interleukin-6 blockade on tissue factor-induced coagulation in human endotoxemia.. Crit Care Med 2004; 32: 1136-1140.
    CrossrefPubMedGoogle Scholar
  • 36 Welty-Wolf KE, Carraway MS, Ortel TL. et al. Blockade of tissue factor-factor X binding attenuates sepsis-induced respiratory and renal failure.. Am J Physiol Lung Cell Mol Physiol 2006; 290: L21-31.
    CrossrefPubMedGoogle Scholar
  • 37 Carraway MS, Welty-Wolf KE, Miller DL. et al. Blockade of tissue factor: Treatment for organ injury in established sepsis.. Am J Respir Crit Care Med 2003; 167: 1200-1209.
    CrossrefPubMedGoogle Scholar
  • 38 Maris NA, de Vos AF, Bresser P. et al. Activation of coagulation and inhibition of fibrinolysis in the lung after inhalation of lipopolysaccharide by healthy volunteers.. Thromb Haemost 2005; 93: 1036-1040.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 de Waard V, Hansen HR, Spronk HH. et al. Differential expression of tissue factor mRNA and protein expression in murine sepsis. The role of the granulocyte revisited.. Thromb Haemost 2006; 95: 348-353.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Carraway MS, Welty-Wolf KE, Miller DL. et al. Blockade of tissue factor: treatment for organ injury in established sepsis.. Am J Respir Crit Care Med 2003; 167: 1200-1209.
    CrossrefPubMedGoogle Scholar
  • 41 Creasey AA, Chang AC, Feigen L. et al. Tissue factor pathway inhibitor reduces mortality from Escherichia coli septic shock.. J Clin Invest 1993; 91: 2850-2860.
    CrossrefPubMedGoogle Scholar
  • 42 Levi M, van der Poll T, ten Cate H. Tissue factor in infection and severe inflammation.. Semin Thromb Hemost 2006; 32: 33-39.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Henriksson CE, Hellum M, Landsverk KS. et al. Flow cytometry-sorted non-viable endotoxin-treated human monocytes are strongly procoagulant.. Thromb Haemost 2006; 96: 29-37.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Henriksson CE, Klingenberg O, Hellum M. et al. Calcium ionophore-induced de-encryption of tissue factor in monocytes is associated with extensive cell death.. Thromb Res 2007; 119: 621-630.
    CrossrefPubMedGoogle Scholar
  • 45 Henriksson CE, Klingenberg O, Ovstebo R. et al. Discrepancy between tissue factor activity and tissue factor expression in endotoxin-induced monocytes is associated with apoptosis and necrosis.. Thromb Haemost 2005; 94: 1236-1244.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Tiruppathi C, Naqvi T, Sandoval R. et al. Synergistic effects of tumor necrosis factor-{alpha} and thrombin in increasing endothelial permeability.. Am J Physiol Lung Cell Mol Physiol 2001; 281 (04) L958-968.
    CrossrefPubMedGoogle Scholar
  • 47 Esmon CT. The protein C pathway.. Chest 2003; 124: 26S-32.
    CrossrefPubMedGoogle Scholar
  • 48 Dhainaut JF, Yan SB, Margolis BD. et al. Drotrecogin alfa (activated) (recombinant human activated protein C) reduces host coagulopathy response in patients with severe sepsis.. Thromb Haemost 2003; 90: 642-653.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 49 Lentz S, Tsiang M, Sadler J. Regulation of thrombomodulin by tumor necrosis factor-alpha: comparison of transcriptional and posttranscriptional mechanisms.. Blood 1991; 77: 542-550.
    PubMedGoogle Scholar
  • 50 Moore KL, Esmon CT, Esmon NL. Tumor necrosis factor leads to the internalization and degradation of thrombomodulin from the surface of bovine aortic endothelial cells in culture.. Blood 1989; 73: 159-165.
    PubMedGoogle Scholar
  • 51 Faust SN, Levin M, Harrison OB. et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis.. N Engl J Med 2001; 345: 408-416.
    CrossrefPubMedGoogle Scholar