Thrombin Activatable Fibrinolysis Inhibitor, a Potential Regulator of Vascular Inflammation *

摘要: The latent plasma carboxypeptidase thrombin-activable fibrinolysis inhibitor (TAFI) is activated by thrombin/thrombomodulin on the endothelial cell surface, and functions in dampening fibrinolysis. In this study, we examined effect of TAFI (TAFIa) modulating proinflammatory bradykinin, complement C5a, thrombin-cleaved osteopontin. Hydrolysis bradykinin C5a osteopontin peptides TAFIa was as efficient that plasmin-cleaved fibrin peptides, indicating these are also good substrates for TAFIa. Plasma N, generally regarded physiological regulator kinins, much less than abrogated C5a-induced neutrophil activation vitro. Jurkat adhesion to markedly enhanced thrombin cleavage This abolished treatment due removal C-terminal Arg168 from exposed SVVYGLR α4β1 integrin-binding site Thus, followed may sequentially up- down-modulate pro-inflammatory properties An engineered anticoagulant thrombin, E229K, able activate endogenous mice, E229K infusion effectively blocked bradykinin-induced hypotension wild-type, but not TAFI-deficient, mice vivo. Our data suggest have a broad anti-inflammatory role, its function restricted