Mechanisms Underlying Coagulation Abnormalities in Ebola Hemorrhagic Fever

Overexpression of Tissue Factor in Primate Monocytes/Macrophages Is a Key Event

Thomas Geisbert, Howard A. Young, Peter B. Jahrling, Kelly J. Davis, Elliott Kagan, Lisa E. Hensley

Research output: Contribution to journalArticle

268 Citations (Scopus)

Abstract

Disseminated intravascular coagulation is a prominent manifestation of Ebola virus (EBOV) infection. Here, we report that tissue factor (TF) plays an important role in triggering the hemorrhagic complications that characterize EBOV infections. Analysis of samples obtained from 25 macaques showed increased levels of TF associated with lymphoid macrophages, whereas analysis of peripheral blood-cell RNA showed increased levels of TF transcripts by day 3. Plasma from macaques contained increased numbers of TF-expressing membrane microparticles. Dysregulation of the fibrinolytic system developed during the course of infection, including a rapid decrease in plasma levels of protein C. Infection of primary human monocytes/macrophages (PHMs) was used to further evaluate the role of TF in EBOV infections. Analysis of PHM RNA at 1-48 h showed increased TF transcripts, whereas levels of TF protein were dramatically increased by day 2. Thus, chemotherapeutic strategies aimed at controlling overexpression of TF may ameliorate the effects of EBOV hemorrhagic fever.

Original languageEnglish (US)
Pages (from-to)1618-1629
Number of pages12
JournalJournal of Infectious Diseases
Volume188
Issue number11
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Ebola Hemorrhagic Fever
Thromboplastin
Primates
Monocytes
Macrophages
Macaca
Ebolavirus
RNA
Disseminated Intravascular Coagulation
Protein C
Infection
Blood Proteins
Blood Cells

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Mechanisms Underlying Coagulation Abnormalities in Ebola Hemorrhagic Fever : Overexpression of Tissue Factor in Primate Monocytes/Macrophages Is a Key Event. / Geisbert, Thomas; Young, Howard A.; Jahrling, Peter B.; Davis, Kelly J.; Kagan, Elliott; Hensley, Lisa E.

In: Journal of Infectious Diseases, Vol. 188, No. 11, 01.12.2003, p. 1618-1629.

Research output: Contribution to journalArticle

Geisbert, Thomas ; Young, Howard A. ; Jahrling, Peter B. ; Davis, Kelly J. ; Kagan, Elliott ; Hensley, Lisa E. / Mechanisms Underlying Coagulation Abnormalities in Ebola Hemorrhagic Fever : Overexpression of Tissue Factor in Primate Monocytes/Macrophages Is a Key Event. In: Journal of Infectious Diseases. 2003 ; Vol. 188, No. 11. pp. 1618-1629.
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