Tissue factor as an initiator of coagulation and inflammation in the lung.
Patients with severe infections almost invariably exhibit evidence of activation of the coagulation system. The lungs are amongst the most frequently affected organs during severe infection and sepsis. The abundant presence of intravascular and extravascular fibrin appears to be a specific hallmark of acute lung injury after sepsis. Tissue factor (TF) is regarded to be the primary initiator of coagulation in severe infection. Effective blockade of the TF pathway, either by recombinant TF pathway inhibitor or by anti-TF antibodies in experimental sepsis, attenuates lung injury and partially prevents pulmonary dysfunction. In addition, inhibition of the activity of TF prevents local activation of coagulation in models of pneumonia. The TF pathway can influence inflammatory signaling by activation of protease activated receptor-1 and -2. This review presents the most recent data on the crosstalk between TF-mediated coagulation and inflammation, with a specific emphasis on these processes in the lung.
van der Poll
Tom
T
Academic Medical Center, University of Amsterdam, Center for Infection and Immunity Amsterdam and Center of Experimental and Molecular Medicine, 1105 AZ Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl
D055371:Acute Lung Injury / Q000097:blood* / Q000209:etiology / Q000473:pathology*; D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D012141:Respiratory Tract Infections / Q000097:blood / Q000209:etiology / Q000473:pathology; D013925:Thromboplastin / Q000502:physiology*
D018836:Inflammation Mediators; D013925:Thromboplastin