The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity.

Abstract

The contact system is a potent procoagulant and proinflammatory plasma protease cascade that is initiated by binding ("contact")-induced, auto-activation of factor XII zymogen. Formed active serine protease FXIIa then cleaves plasma prekallikrein to kallikrein that in turn liberates the mediator bradykinin from its precursor high molecular weight kininogen. Bradykinin induces inflammation with implications for host defense and innate immunity. FXIIa also triggers the intrinsic pathway of coagulation that has been shown to critically contribute to thrombosis. Vice versa, FXII deficiency impairs thrombosis in animal models without inducing abnormal excessive bleeding. Recent work has established the FXIIa-driven contact system as promising target for anticoagulant and anti-inflammatory drugs. This review focuses on the biochemistry of the contact system, its regulation by endogenous and exogenous inhibitors, and roles in disease states. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John.

• Authors: Henri Weidmann, Laura Heikaus, Andy T Long, Clément Naudin, Hartmut Schlüter, Thomas Renné
• Journal: Biochimica et biophysica acta. Molecular cell research (Biochim Biophys Acta Mol Cell Res) Vol. 1864 Issue 11 Pt B Pg. 2118-2127 (Nov 2017) ISSN: 0167-4889 [Print] Netherlands
• PMID: 28743596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Kallikreins
• Factor XIIa
• Bradykinin

Topics

• Blood Coagulation (genetics)
• Bradykinin (genetics)
• Factor XII Deficiency (blood, genetics, pathology)
• Factor XIIa (genetics)
• Humans
• Immunity, Innate (genetics)
• Inflammation (blood, genetics, pathology)
• Kallikreins (genetics)
• Thrombosis (blood, genetics, pathology)