title: Contact system revisited: an interface between inflammation, coagulation, and innate immunity.
abstract: The contact system is a plasma protease cascade initiated by factor XII (FXII) that activates the proinflammatory kallikrein-kinin system and the procoagulant intrinsic coagulation pathway. Anionic surfaces induce FXII zymogen activation to form proteolytically active FXIIa. Bacterial surfaces also have the ability to activate contact system proteins, indicating an important role for host defense using the cooperation of the inflammatory and coagulation pathways. Recent research has shown that inorganic polyphosphate found in platelets activates FXII in vivo and can induce coagulation in pathological thrombus formation. Experimental studies have shown that interference with FXII provides thromboprotection without a therapy-associated increase in bleeding, renewing interest in the FXIIa-driven intrinsic pathway of coagulation as a therapeutic target. This review summarizes how the contact system acts as the cross-road of inflammation, coagulation, and innate immunity.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: A T
authors.initials: AT
authors.lastname: Long
authors.affiliation: Division of Clinical Chemistry, Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Kenne
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Jung
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Division of Clinical Chemistry, Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: T A
authors.initials: TA
authors.lastname: Fuchs
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Division of Clinical Chemistry, Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet and University Hospital, Stockholm, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Renné
mesh_terms: D054179:Angioedemas, Hereditary / Q000097:blood / Q000276:immunology; D000818:Animals; D001777:Blood Coagulation; D005174:Factor XII / Q000378:metabolism*; D022781:Hepatocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000097:blood* / Q000276:immunology*; D018836:Inflammation Mediators / Q000097:blood* / Q000276:immunology*; D011122:Polyphosphates / Q000097:blood; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood / Q000276:immunology
chemical_list: D018836:Inflammation Mediators; D011122:Polyphosphates; D005174:Factor XII
keywords: angioedema; anticoagulation; factor XII; inflammation; polyphosphates; thrombosis