title: Mechanisms underlying coagulation abnormalities in ebola hemorrhagic fever: overexpression of tissue factor in primate monocytes/macrophages is a key event.
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.
authors.affiliation: Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA 21702-5011. tom.geisbert@amedd.army.mil.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.forename: Peter B
authors.initials: PB
authors.lastname: Jahrling
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Davis
authors.forename: Elliott
authors.initials: E
authors.lastname: Kagan
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Hensley
mesh_terms: D000818:Animals; D004211:Disseminated Intravascular Coagulation / Q000209:etiology*; D005337:Fibrin / Q000378:metabolism; D019142:Hemorrhagic Fever, Ebola / Q000150:complications*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013925:Thromboplastin / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D005337:Fibrin; D013925:Thromboplastin