Local activation of the tissue factor-factor VIIa pathway in patients with pneumonia and the effect of inhibition of this pathway in murine pneumococcal pneumonia.
OBJECTIVE
The tissue factor (TF)-factor VIIa (FVIIa) complex not only is essential for activation of blood coagulation but also affect the inflammatory response during sepsis. The objective of this study was to determine the role of TF-FVIIa in pneumonia caused by Streptococcus pneumoniae, the most important causative organism in community-acquired pneumonia and a major cause of sepsis.


METHODS
A controlled, in vivo laboratory study.


METHODS
Research laboratory of a health sciences university.


METHODS
Patients with unilateral community-acquired pneumonia and female BALB/c mice.


METHODS
Bilateral bronchoalveolar lavage was performed in patients with community-acquired pneumonia. In mice, pneumonia was induced by intranasal inoculation with S. pneumoniae with or without concurrent inhibition of TF-FVIIa by subcutaneous injections of recombinant nematode anticoagulant protein (rNAPc2).


RESULTS
Patients with unilateral community-acquired pneumonia demonstrated elevated concentrations of FVIIa, soluble TF, and thrombin-antithrombin complexes in bronchoalveolar lavage fluid obtained from the infected site compared with the uninfected site. Mice with S. pneumoniae pneumonia displayed increased TF expression and fibrin deposits in lungs together with elevated thrombin-antithrombin complex levels in bronchoalveolar lavage fluid; inhibition of TF-FVIIa by rNAPc2 attenuated the procoagulant response in the lung but did not affect host defense, as reflected by an unaltered outgrowth of pneumococci and an unchanged survival.


CONCLUSIONS
These data suggest that TF-FVIIa activity contributes to activation of coagulation in the lung during pneumococcal pneumonia but does not play an important role in the antibacterial host defense in this murine model.
Rijneveld
Anita W
AW
Center of Infection and Immunity Amsterdam, Laboratory of Experimental Internal Medicine, Department of Pulmonology, University of Amsterdam, the Netherlands.
Weijer
Sebastiaan
S
Bresser
Paul
P
Florquin
Sandrine
S
Vlasuk
George P
GP
Rote
William E
WE
Spek
C Arnold
CA
Reitsma
Pieter H
PH
van der Zee
Jaring S
JS
Levi
Marcel
M
van der Poll
Tom
T
D000328:Adult; D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004195:Disease Models, Animal; D015942:Factor VIIa / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D015801:Helminth Proteins / Q000008:administration & dosage; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy / Q000378:metabolism* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000302:isolation & purification; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism*
D015801:Helminth Proteins; C108605:anti-coagulant protein 5, Ancylostoma caninum; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D015942:Factor VIIa