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Thromb Haemost 2000; 83(01): 114-118
DOI: 10.1055/s-0037-1613766
Commentary
Schattauer GmbH

Induction of Tissue Factor Procoagulant Activity in Myelomonocytic Cells Inoculated by the Agent of Human Granulocytic Ehrlichiosis

Rajesh Behl
1   From the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
,
Marina B. Klein
1   From the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
,
Luke Dandelet
1   From the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
,
Ronald R. Bach
2   Research Service, Veterans’ Administration Medical Center, Minneapolis, MN, USA
,
Jesse L. Goodman
1   From the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
,
Nigel S. Key
1   From the Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
› Author Affiliations
Further Information

Publication History

Received 17 June 1999

Accepted after revision 02 September 1999

Publication Date:
06 December 2017 (online)

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Summary

Human granulocytic ehrlichiosis (HGE) is a recently recognized rickettsial tick-borne febrile illness that may occasionally be complicated by coagulopathy. The agent of HGE (aHGE) is an obligate intracellular pathogen, which replicates in endosomes within neutrophils and their precursors. We hypothesized that aHGE might cause DIC via induction of monocyte tissue factor procoagulant activity (TF PCA). Peripheral blood mononuclear cells (PBMNC) and HL-60 cells were used to model the effect of aHGE infection on monocytes/macrophages. Mononuclear cells inoculated with aHGE in vitro demonstrated approximately a 12-15-fold increase in TF PCA, with peak activity occurring at 8-12 h. HL-60 cells inoculated with aHGE also manifested a 4-6 fold induction of TF PCA, with maximal activity occurring at about 8 h. By comparison, E. Coli lipopolysaccharide (LPS) also induced an increase in TF PCA of an equivalent magnitude, and with a similar time course. Induction of TF did not require inoculation of HL-60 cells with live organism, since heat-inactivated aHGE still stimulated TF PCA expression in the target cells. Furthermore, filtered supernatants from heat-inactivated organisms induced TF PCA suggesting that the effect is due to a soluble mediator produced by the organism. Although aHGE is a gram negative organism, the soluble mediator did not appear to be classic endotoxin in that the supernatants tested negative for endotoxin by the Limulus Amoebocyte assay, and polymixin had no inhibitory effect on aHGE supernatants. We conclude that aHGE induces cells of the myelo-monocytic lineage to synthesize TF, which may contribute to the clinical coagulopathy that can be observed in this condition. An atypical soluble mediator or cellular component of the organism appears to be critically important in TF induction by aHGE.

Key words

Human granulocytic ehrlichiosis - monocyte - tissue Factor - HL-60 - lipopolysaccharide
 

  • References

  • 1 Bakken JS, Krueth J, Wilson-Nordskog C, Tilden RL, Asanovich K, Dumler JS. Clinical and laboratory characteristics of human granulocytic ehrlichiosis. JAMA 1996; 275 (03) 199-205.
    CrossrefPubMedGoogle Scholar
  • 2 Maeda K, Markowitz N, Hawley RC, Ristic M, Cox D, McDade JE. Human infection with Ehrlichia canis, a leukocytic rickettsia. N Engl J Med 1987; 316 (14) 853-6.
    CrossrefPubMedGoogle Scholar
  • 3 Foggie A. Studies on the infectious agent of tick-borne fever in sheep. J Pathol Bacteriol 1951; 53: 1.
    PubMedGoogle Scholar
  • 4 Rikihisa Y. The tribe Ehrlichieae and ehrlichial diseases. Clin Microbiol Rev 1991; 04 (03) 286-308.
    CrossrefPubMedGoogle Scholar
  • 5 Walker DH, Dumler JS. Human monocytic and granulocytic ehrlichioses. Discovery and diagnosis of emerging tick-borne infections and the critical role of the pathologist. Arch Pathol Lab Med 1997; 121 (08) 785-91.
    PubMedGoogle Scholar
  • 6 Goodman JL, Nelson C, Vitale B, Madigan JE, Dumler JS, Kurtti TJ, Munderloh UG. Direct cultivation of the causative agent of human granulocytic ehrlichiosis. N Engl J Med 1996; 334 (04) 209-15.
    CrossrefPubMedGoogle Scholar
  • 7 Klein MB, Miller JS, Nelson CM, Goodman JL. Primary bone marrow progenitors of both granulocytic and monocytic origin are susceptible to infection with the agent of human granulocytic ehrlichiosis. JID 1997; 176 (05) 1405-9.
    CrossrefPubMedGoogle Scholar
  • 8 Carey MJ, Rodgers GM. Disseminated intravascular coagulation: clinical and laboratory aspects. Am J Hematol 1998; 59 (01) 65-73.
    CrossrefPubMedGoogle Scholar
  • 9 Semeraro N, Colucci M. Tissue factor in health and disease. Thromb Haemost 1997; 78 (01) 759-64.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Bach R, Gentry R, Nemerson Y. Factor VII binding to tissue factor in reconstituted phospholipid vesicles: induction of cooperativity by phosphatidylserine. Biochemistry 1986; 25 (14) 4007-20.
    CrossrefPubMedGoogle Scholar
  • 11 Carson SD, Ross SE, Bach R, Guha A. An inhibitory monoclonal antibody against human tissue factor. Blood 1987; 70 (02) 490-3.
    PubMedGoogle Scholar
  • 12 Fichtenbaum CJ, Peterson LR, Weil GJ. Ehrlichiosis presenting as a lifethreatening illness with features of the toxic shock syndrome. Am J Med 1993; 95 (04) 351-7.
    CrossrefPubMedGoogle Scholar
  • 13 Marty AM, Dumler JS, Imes G, Brusman HP, Smrkovski LL, Frisman DM. Ehrlichiosis mimicking thrombotic thrombocytopenic purpura. Case report and pathological correlation. Hum Pathol 1995; 26 (08) 920-5.
    CrossrefPubMedGoogle Scholar
  • 14 Arraga-Alvarado C, Montero-Ojeda M, Bernardoni A, Anderson BE, Parra O. Human ehrlichiosis: report of the first case in Venezuela. Investigacion Clinica 1996; 37 (01) 35-49.
    PubMedGoogle Scholar
  • 15 Winslow GM, Yager E, Shilo K, Collins DN, Chu FK. Infection of the laboratory mouse with the intracellular pathogen Ehrlichia chaffeensis. Infection and Immunity 1998; 66 (08) 3892-9.
    PubMedGoogle Scholar
  • 16 ten Cate JW, van der Poll T, Levi M, ten Cate H, van Deventer SJ. Cytokines: triggers of clinical thrombotic disease. Thromb Haemost 1997; 78 (01) 415-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Levi M, ten Cate H, van der Poll T, van Deventer SJ. Pathogenesis of disseminated intravascular coagulation in sepsis. JAMA 1993; 270 (08) 975-9.
    CrossrefPubMedGoogle Scholar
  • 18 Taylor Jr FB. Role of tissue factor and factor VIIa in the coagulant and inflammatory response to LD100 Escherichia coli in the baboon. Haemostasis 26 Suppl 1996; 01: 83-91.
    PubMedGoogle Scholar
  • 19 Rivers RP, Hathaway WE, Weston WL. The endotoxin-induced coagulant activity of human monocytes. Brit J Haem 1975; 30 (03) 311-6.
    CrossrefPubMedGoogle Scholar
  • 20 Moore KL, Andreoli SP, Esmon NL, Esmon CT, Bang NU. Endotoxin enhances tissue factor and suppresses thrombomodulin expression of human vascular endothelium in vitro. J Clin Invest 1987; 79 (01) 124-30.
    CrossrefPubMedGoogle Scholar
  • 21 Bevilacqua MP, Pober JS, Majeau GR, Fiers W, Cotran RS, Gimbrone Jr MA. Recombinant tumor necrosis factor induces procoagulant activity in cultured vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci 1986; 83 (12) 4533-7.
    CrossrefPubMedGoogle Scholar
  • 22 Sporn LA, Haidaris PJ, Shi RJ, Nemerson Y, Silverman DJ, Marder VJ. Rickettsia rickettsii infection of cultured human endothelial cells induces tissue factor expression. Blood 1994; 83 (06) 1527-34.
    PubMedGoogle Scholar
  • 23 Miragliotta G, Marcuccio C, Miragliotta G, Fumarola D, Colucci M, Semararo N. Platelet aggregation and stimulation of leukocyte procoagulant activity by rickettsial lipopolysaccharides in rabbits and in man. Experimentia 1981; 37 (01) 47-9.
    CrossrefPubMedGoogle Scholar
  • 24 Klein MB, Hayes SF, Goodman JL. Monocytic differentiation inhibits infection and granulocytic differentiation potentiates infection by the agent of human granulocytic ehrlichiosis. Infection and Immunity 1998; 66 (07) 3410-5.
    PubMedGoogle Scholar
  • 25 Neumann FJ, Ott I, Marx N, Luther T, Kenngott S, Gawaz M, Kotzsch M, Schomig A. Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity. Arterioscler Thromb Vasc Biol 1997; 17 (12) 3399-405.
    CrossrefPubMedGoogle Scholar
  • 26 Schecter AD, Rollins BJ, Zhang YJ, Charo IF, Fallon JT, Rossikhina M, Giesen PL, Nemerson Y, Taubman MB. Tissue factor is induced by monocyte chemoattractant protein-1 in human aortic smooth muscle and THP-1 cells. J Biol Chem 1997; 272 (45) 28568-73.
    CrossrefPubMedGoogle Scholar
  • 27 Ernofsson M, Siegbahn A. Platelet-derived growth factor-BB and monocyte chemotactic protein-1 induce human peripheral blood monocytes to express tissue factor. Thromb Res 1996; 83 (04) 307-20.
    CrossrefPubMedGoogle Scholar
  • 28 Luster AD. Chemokines-chemotactic cytokines that mediate inflammation. N Engl J Med 1998; 338 (07) 436-45.
    CrossrefPubMedGoogle Scholar
  • 29 Mackman N. Regulation of the tissue factor gene. Thromb Haemost 1997; 78 (01) 747-54.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Bloem LJ, Chen L, Konigsberg WH, Bach R. Serum stimulation of quiescent human fibroblasts induces the synthesis of tissue factor mRNA followed by the appearance of tissue factor antigen and procoagulant activity. J Cellular Physiol 1989; 139 (02) 418-23.
    CrossrefPubMedGoogle Scholar
  • 31 Bach RR, Moldow CF. Mechanism of tissue factor activation on HL-60 cells. Blood 1998; 89 (09) 3270-6.
    PubMedGoogle Scholar
  • 32 Lee EH, Rikihisa Y. Absence of tumor necrosis factor-alpha, interleukin 6 (IL-6), and granulocyte-macrophage colony-stimulating factor expression but presence of IL-1beta, IL-8, and IL-10 expression in human monocytes exposed to viable or heat killed Ehrlichia chaffeensis. Infection and Immunity 1996; 64 (10) 4211-9.
    PubMedGoogle Scholar