Activation of coagulation and inhibition of fibrinolysis in the human lung on bronchial instillation of lipoteichoic acid and lipopolysaccharide.
OBJECTIVE
Pneumonia is characterized by an acute inflammatory response in the lung, which is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. Here, we compared the effects of lipoteichoic acid (LTA), a major cell wall component of Gram-positive bacteria, and lipopolysaccharide (LPS), in the human bronchoalveolar space.


METHODS
Controlled in vivo volunteer study.


METHODS
Clinical research unit.


METHODS
Twenty-three healthy nonsmoking male volunteers.


METHODS
Sterile saline was instilled into a lung subsegment followed by bronchoscopic instillation of either LTA (Staphylococcus aureus, at a dose of 4, 20, or 100 ng/kg body weight) or LPS (Escherichia coli, 4 ng/kg body weight) into the contralateral lung. Bronchoalveolar lavage fluid was obtained 6 hours thereafter.


RESULTS
Bronchial instillation of LTA- or LPS-activated bronchoalveolar coagulation, as reflected by increases in the levels of thrombin-antithrombin complexes, d-dimer, and soluble tissue factor. Concurrently, LTA and LPS inhibited anticoagulant mechanisms, as indicated by reductions in antithrombin, Protein C, and Activated Protein C concentrations together with elevated levels of soluble thrombomodulin. Both LTA and LPS administration was associated with an inhibition of pulmonary fibrinolysis, as measured by a reduction in plasminogen activator activity and elevated levels of plasminogen activator inhibitor type I.


CONCLUSIONS
This study is the first to describe the effects of LTA on hemostasis in humans, demonstrating that LTA induces similar changes in the human bronchoalveolar space as LPS, characterized by activation of coagulation with concurrent inhibition of anticoagulant and fibrinolytic pathways.
Hoogerwerf
Jacobien J
JJ
Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.j.hoogerwerf@amc.uva.nl
de Vos
Alex F
AF
Levi
Marcel
M
Bresser
Paul
P
van der Zee
Jaring S
JS
Draing
Christian
C
von Aulock
Sonja
S
van der Poll
Tom
T
D001777:Blood Coagulation / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid; D004305:Dose-Response Relationship, Drug; D005342:Fibrinolysis / Q000187:drug effects*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D013682:Teichoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D013925:Thromboplastin / Q000378:metabolism; D055815:Young Adult
D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid; D013925:Thromboplastin