Regulation of tissue inflammation by thrombin-activatable carboxypeptidase B (or TAFI).

Molecular Immunology
Lawrence L LeungWilliam H Robinson

Abstract

Thrombin-activatable procarboxypeptidase B (proCPB or thrombin-activatable fibrinolysis inhibitor or TAFI) is a plasma procarboxypeptidase that is activated by the thrombin-thrombomodulin complex on the vascular endothelial surface. The activated CPB removes the newly exposed carboxyl terminal lysines in the partially digested fibrin clot, diminishes tissue plasminogen activator and plasminogen binding, and protects the clot from premature lysis. We have recently shown that CPB is catalytically more efficient than plasma CPN, the major plasma anaphylatoxin inhibitor, in inhibiting bradykinin, activated complement C3a, C5a, and thrombin-cleaved osteopontin in vitro. Using a thrombin mutant (E229K) that has minimal procoagulant properties but retains the ability to activate protein C and proCPB in vivo, we showed that infusion of E229K thrombin into wild-type mice reduced bradykinin-induced hypotension but it had no effect in proCPB-deficient mice, indicating that the beneficial effect of E229K thrombin is mediated through its activation of proCPB and not protein C. Similarly proCPB-deficient mice displayed enhanced pulmonary inflammation in a C5a-induced alveolitis model and E229K thrombin ameliorated the magnitude of alveolitis...Continue Reading

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Citations

May 30, 2009·Molecular Biology of the Cell·Gene L GarciaCarole A Parent
Jan 30, 2010·Critical Care Medicine·Hartmut Weiler
Sep 20, 2011·The Journal of Clinical Investigation·Bianca WoehrlDiederik van de Beek
Mar 28, 2012·Journal of Biomedical Science·Yi-Heng LiHua-Lin Wu
Jun 2, 2011·Hämostaseologie·P J Declerck
Dec 12, 2013·Journal of Clinical Immunology·Lu LiuGuolan Xing
Jan 26, 2016·Seminars in Hematology·Tine WyseureAnnette von Drygalski
Jan 11, 2012·Clinics and Research in Hepatology and Gastroenterology·Abdurrahim SayilirMehmet Ibiş
Jan 23, 2014·Arthritis & Rheumatology·Christin M LepusWilliam H Robinson
Jul 30, 2014·Journal of Thrombosis and Haemostasis : JTH·T PlugJ C M Meijers
Jan 22, 2010·Journal of Thrombosis and Haemostasis : JTH·L QinE C Gabazza
Sep 2, 2009·Journal of Thrombosis and Haemostasis : JTH·J L WillemseD F Hendriks
Nov 18, 2015·Blood Reviews·Toshiaki IbaJecko Thachil
Jun 3, 2014·Drug Discovery Today·Tine Wyseure, Paul J Declerck
Jun 11, 2011·Blood·Laurent O Mosnier
Aug 20, 2016·Nature Reviews. Rheumatology·William H RobinsonJeremy Sokolove
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Mar 5, 2016·The Journal of Rheumatology·Stefan EdgintonHani El-Gabalawy

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