The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity
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The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity. / Weidmann, Henri; Heikaus, Laura; Long, Andy T; Naudin, Clément; Schlüter, Hartmut; Renné, Thomas.
in: BBA-MOL CELL RES, Jahrgang 1864, Nr. 11 Pt B, 11.2017, S. 2118-2127.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity
AU - Weidmann, Henri
AU - Heikaus, Laura
AU - Long, Andy T
AU - Naudin, Clément
AU - Schlüter, Hartmut
AU - Renné, Thomas
N1 - Copyright © 2017. Published by Elsevier B.V.
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
KW - Journal Article
KW - Review
U2 - 10.1016/j.bbamcr.2017.07.009
DO - 10.1016/j.bbamcr.2017.07.009
M3 - SCORING: Journal article
C2 - 28743596
VL - 1864
SP - 2118
EP - 2127
JO - BBA-MOL CELL RES
JF - BBA-MOL CELL RES
SN - 0167-4889
IS - 11 Pt B
ER -