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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1992-1997. Prepublished online as a Blood First Edition Paper on November 14, 2006; DOI 10.1182/blood-2006-03-012567. This Article Full Text Full Text (PDF) Erratum (v109,p3632) All Versions of this Article: blood-2006-03-012567v1 109/5/1992    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nishimura, T. Articles by Leung, L. L. K. Search for Related Content PubMed PubMed Citation Articles by Nishimura, T. Articles by Leung, L. L. K. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Thrombin-activatable procarboxypeptidase B regulates activated complement C5a in vivo Toshihiko Nishimura3, Timothy Myles1, Adrian M. Piliposky2, Peter N. Kao3, Gerald J. Berry2, and Lawrence L. K. Leung1 1 Department of Medicine, Stanford University School of Medicine and Veterans Administration Palo Alto Health Care System, Palo Alto, CA; 2 Department of Pathology, Stanford University School of Medicine and Veterans Administration Palo Alto Health Care System, Palo Alto, CA; 3 Department of Pulmonary and Critical Care Medicine, Stanford University School of Medicine and Veterans Administration Palo Alto Health Care System, Palo Alto, CA Plasma procarboxypeptidase B (proCPB) is activated by the endothelial thrombin-prothrombomodulin complex. Activated (CPB) functions as a fibrinolysis inhibitor, but it may play a broader role by inactivating inflammatory mediators. To test this hypothesis, C5a-induced alveolitis was studied in wild-type (WT) and proCPB-deficient mice (proCPB–/–). C5a-induced alveolitis, as measured by cell counts and total protein contents in bronchoalveolar lavage fluids, was markedly enhanced in the proCPB–/– mice. E229K thrombin, a thrombin mutant with minimal clotting activity but retaining its ability to activate protein C and proCPB, attenuated C5a-induced alveolitis in WT but not in proCPB–/– mice, indicating that its beneficial effect is mediated primarily by its activation of proCPB. Lung tissue histology confirmed these cellular inflammatory responses. Delayed administration of E229K thrombin after the C5a instillation was ineffective in reducing alveolitis in WT mice, suggesting that the beneficial effect of E229K thrombin is due to the direct inhibition of C5a by CPB. Our studies show that thrombin-activatable proCPB, in addition to its role in fibrinolysis, has intrinsic anti-inflammatory functions. Its activation, along with protein C, by the endothelial thrombin-TM complex represents a homeostatic response to counteract the inflammatory mediators generated at the site of vascular injury. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. O. Mosnier, X. V. Yang, and J. H. Griffin Activated Protein C Mutant with Minimal Anticoagulant Activity, Normal Cytoprotective Activity, and Preservation of Thrombin Activable Fibrinolysis Inhibitor-dependent Cytoprotective Functions J. Biol. Chem., November 9, 2007; 282(45): 33022 - 33033. [Abstract] [Full Text] [PDF]

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