TY - JOUR T1 - Role of thrombin-activatable fibrinolysis inhibitor in lipopolysaccharide-induced acute lung injury JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - p4093 AU - Masahiro Naito AU - Osamu Taguchi AU - Takehiro Takagi AU - Tetsu Kobayashi AU - Corina D'Alessandro-Gabazza AU - Esteban Gabazza Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/p4093.abstract N2 - Background: In acute lung injury, excessive coagulation induced by inflammatory responses may feedback to further increase the inflammatory response and promote fibrosis. Thrombin-activatable fibrinolysis inhibitor (TAFI) is mainly synthesized in the liver and circulates in the bloodstream as an inactive proenzyme. It can be activated by the thrombin-thrombomodulin complex to a carboxypeptidase (TAFIa), which acts as an anti-fibrinolytic factor by inhibiting the activation of plasmin through the removal of carboxy-terminal lysines from fibrin. Recent studies have shown that TAFIa can also regulate inflammatory responses by its ability to inhibit complement C3a and C5a, and osteopontin.Objective: Our aim was to evaluate the effect of TAFI on acute lung injury in the mouse.Methods: Acute lung injury was induced in wild type and TAFI deficient (KO) C57/BL6 mice by intratracheal instillation of lipopolysaccharide (LPS:5mg/kg). Mice treated with saline served as controls. We compared the inflammatory response to LPS in both groups. Animals were sacrificed 24 hours after LPS injection and broncho-alveolar lavage fluid (BALF) was sampled.Results: TAFI KO mice had worse acute lung injury as their total protein, total cell count, and levels of IL-1β, IL-6 and TNF-α were increased in BALF in LPS-treated TAFI KO mice compared to wild type. The increase in cells in BALF was due to an increase in neutrophils. Complement C5a in both BALF and plasma was increased in LPS-treated TAFI KO mice compared to wild type.Conclusions: These results suggest that TAFI protects against acute lung injury at least partially through its ability to inactivate complement C5a. ER -