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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
 

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