Activation of coagulation and inhibition of fibrinolysis in the lung after inhalation of lipopolysaccharide by healthy volunteers.
Pneumonia is frequently associated with changes in coagulation and fibrinolysis in the bronchoalveolar space. To determine the effect of lipopolysaccharide (LPS) on the hemostatic balance in the human lung, six healthy subjects inhaled nebulized LPS or saline in a randomized cross-over study and bronchoalveolar lavage fluid was obtained six hours thereafter. LPS induced soluble tissue factor and thrombin-antithrombin complexes and inhibited plasminogen activator activity in BALF. Additionally plasminogen activator inhibitor type 1 production was upregulated after LPS inhalation. LPS also elicited local activation of neutrophils (release of elastase, myeloperoxidase and bactericidal/permeability increasing protein) and secretion of interleukin (IL)-6 and IL-8. Inhalation of LPS by healthy humans reproduces major features of the procoagulant response to inflammatory and infectious lung diseases and may be used as a novel model to evaluate pathogenetic mechanisms and new interventions.
Maris
Nico A
NA
Department of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
de Vos
Alex F
AF
Bresser
Paul
P
van der Zee
Jaring S
JS
Meijers
Joost C
JC
Lijnen
H Roger
HR
Levi
Marcel
M
Jansen
Henk M
HM
van der Poll
Tom
T
D000280:Administration, Inhalation; D000328:Adult; D000990:Antithrombin III / Q000096:biosynthesis; D001777:Blood Coagulation / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018592:Cross-Over Studies; D016207:Cytokines / Q000096:biosynthesis; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000209:etiology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008168:Lung / Q000098:blood supply / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010447:Peptide Hydrolases / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis; D013925:Thromboplastin / Q000096:biosynthesis
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D017395:Plasminogen Activator Inhibitor 1; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases