Inhibition of the tissue factor/factor VIIa pathway does not influence the inflammatory or antibacterial response to abdominal sepsis induced by Escherichia coli in mice.
BACKGROUND
Anticoagulants have gained increasing attention for the treatment of sepsis. Inhibition of the tissue factor (TF)/factor (F) VIIa pathway has been shown to attenuate the activation of coagulation and to prevent death in a primate model of sepsis caused by gram-negative bacteria.


METHODS
To determine the role of the TF/FVIIa complex in the host response to peritonitis, mice received an intraperitoneal injection of live Escherichia coli with or without concurrent treatment with recombinant nematode anticoagulant protein c2 (rNAPc2), a selective inhibitor of the TF/FVIIa pathway.


RESULTS
Peritonitis was associated with an increase in the expression of TF at the tissue level and activation of coagulation, as reflected by elevated levels of thrombin-antithrombin complexes and by increased fibrin(ogen) deposition in the liver and lungs. rNAPc2 strongly attenuated this procoagulant response but did not influence the inflammatory response (histopathology, leukocyte recruitment to the peritoneal cavity, and cytokine and chemokine levels). Moreover, rNAPc2 did not alter bacterial outgrowth locally or dissemination of the infection, and survival was not different between rNAPc2-treated mice and control mice.


CONCLUSIONS
These data suggest that TF/FVIIa activity contributes to the activation of coagulation during E. coli peritonitis but does not play a role in the inflammatory response or antibacterial host defense.
Weijer
Sebastian
S
Laboratory of Experimental Internal Medicine and Department of Infectious Diseases, Tropical Medicine, and AIDS, University of Amsterdam, The Netherlands. s.weijer@amc.uva.nl.
Schoenmakers
Saskia H H F
SH
Florquin
Sandrine
S
Levi
Marcel
M
Vlasuk
George P
GP
Rote
William E
WE
Reitsma
Pieter H
PH
Spek
C Arnold
CA
van der Poll
Tom
T
D000818:Animals; D001777:Blood Coagulation; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development*; D004927:Escherichia coli Infections / Q000382:microbiology*; D015942:Factor VIIa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015801:Helminth Proteins / Q000008:administration & dosage / Q000235:genetics; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000276:immunology / Q000382:microbiology* / Q000503:physiopathology; D013925:Thromboplastin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D015801:Helminth Proteins; C400226:anti-coagulant protein C2, Ancylostoma caninum; D013925:Thromboplastin; D015942:Factor VIIa