Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation.

The Journal of Clinical Investigation
Coen MaasMartijn F B G Gebbink

Abstract

When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the kallikrein-kinin system). However, while Factor XII is important for coagulation in vitro, it is not important for physiological hemostasis, so the physiological role of the contact system remains elusive. Using patient blood samples and isolated proteins, we identified a novel class of Factor XII activators. Factor XII was activated by misfolded protein aggregates that formed by denaturation or by surface adsorption, which specifically led to the activation of the kallikrein-kinin system without inducing coagulation. Consistent with this, we found that Factor XII, but not Factor XI, was activated and kallikrein was formed in blood from patients with systemic amyloidosis, a disease marked by the accumulation and deposition of misfolded plasma proteins. These results show that the kallikrein-kinin system can be activated by Factor XII, in a process separate from the coagulation cascade, and point to a protective role for Factor XII following activ...Continue Reading

References

Sep 2, 1991·Science·D Gailani, G J Broze
Sep 1, 1974·The Journal of Experimental Medicine·D C Morrison, C G Cochrane
Jan 1, 1983·The Journal of Clinical Investigation·F van der GraafB N Bouma
Jan 1, 1984·Thrombosis Research·A H SchmaierR W Colman
Sep 1, 1980·The Journal of Experimental Medicine·J G CurdC G Cochrane
May 13, 1998·Archives of Disease in Childhood. Fetal and Neonatal Edition·J SonntagM Obladen
Jul 3, 1998·Alzheimer Disease and Associated Disorders·L BergamaschiniA Agostoni
Dec 5, 1998·Mediators of Inflammation·J SonntagM Obladen
Jan 13, 1999·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Y ShibayamaA P Kaplan
Oct 9, 2001·Mechanisms of Ageing and Development·L BergamaschiniV Gallai
Jan 10, 2002·The Journal of Biological Chemistry·Maarten F M EngelAntonie J W G Visser
Oct 3, 2002·The Journal of Biological Chemistry·Min ZhuAnthony L Fink
Nov 7, 2002·Current Biology : CB·Onno KranenburgMartijn F B G Gebbink
Dec 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Christopher P JaroniecRobert G Griffin
Aug 12, 2003·The Journal of Biological Chemistry·Barend BoumaMartijn F B G Gebbink
Apr 1, 1955·The Journal of Clinical Investigation·O D RATNOFF, J E COLOPY
Apr 20, 2004·Cellular and Molecular Life Sciences : CMLS·T Syrovets, Th Simmet
Aug 5, 2004·Pharmaceutical Research·Satomi OnoueTakehiko Yajima
Apr 29, 2005·The Journal of Biological Chemistry·Martin KarlssonUno Carlsson
Jul 1, 2005·Langmuir : the ACS Journal of Surfaces and Colloids·Maarten F M EngelCarlo P M van Mierlo
Jul 26, 2005·Journal of Chromatography. a·Alois JungbauerRainer Hahn
Feb 10, 2006·Blood Cells, Molecules & Diseases·Thomas RennéDavid Gailani
Feb 25, 2006·Biological Chemistry·Julia JohneThomas Renné
Jun 8, 2006·Annual Review of Biochemistry·Fabrizio Chiti, Christopher M Dobson
Sep 9, 2006·Current Opinion in Lipidology·Geoffrey J Howlett, Kathryn J Moore
Sep 28, 2006·Thrombosis and Haemostasis·Jinan LiTor Ny
Dec 1, 2006·The Journal of Biological Chemistry·Coen MaasMartijn F B G Gebbink
Dec 23, 2006·American Journal of Human Genetics·Sven CichonMarkus M Nöthen
Mar 21, 2007·Journal of Thrombosis and Haemostasis : JTH·B BoumaM F B G Gebbink
Mar 29, 2007·Journal of Thrombosis and Haemostasis : JTH·G EndlerC Mannhalter
May 19, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Eszter HerczenikJan-Willem N Akkerman
Aug 29, 2007·Journal of Thrombosis and Haemostasis : JTH·J W P Govers-RiemslagH ten Cate

❮ Previous
Next ❯

Citations

Aug 23, 2011·Seminars in Immunopathology·Thomas Renné
Mar 16, 2011·Journal of Thrombosis and Thrombolysis·Rebecca S WoodruffRichard C Becker
Jun 11, 2010·Current Diabetes Reports·Edward P Feener
May 5, 2010·Proceedings of the National Academy of Sciences of the United States of America·Coen MaasRolf T Urbanus
Jan 10, 2013·Investigative Ophthalmology & Visual Science·Jia LiuEdward P Feener
Aug 30, 2008·The Journal of Clinical Investigation·Alvin H Schmaier
Dec 12, 2012·PloS One·Julia GanslerKlaus T Preissner
Sep 10, 2013·PloS One·Joke KoningsJosé W P Govers-Riemslag
May 1, 2010·Current Cardiology Reports·Becky WoodruffRichard C Becker
Nov 14, 2015·Journal of Thrombosis and Haemostasis : JTH·Alvin H Schmaier
Mar 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Daria ZamolodchikovSidney Strickland
Jan 15, 2013·Current Opinion in Microbiology·Kelly Schwartz, Blaise R Boles
Sep 17, 2015·Journal of Internal Medicine·E KenneT Renné
Oct 31, 2012·Research in Microbiology·William H DePas, Matthew R Chapman
Mar 9, 2012·Thrombosis Research·Coen Maas, Thomas Renné
Oct 24, 2009·Thrombosis Research·Alvin H Schmaier
Dec 29, 2015·Journal of Thrombosis and Haemostasis : JTH·Andrew T LongThomas Renné
Dec 5, 2008·Journal of Thrombosis and Haemostasis : JTH·V PönitzUNKNOWN RACS Study Group
May 4, 2011·Journal of Thrombosis and Haemostasis : JTH·N J Mutch
Apr 13, 2011·Journal of Thrombosis and Haemostasis : JTH·E KilinçH M H Spronk
May 11, 2013·Journal of Thrombosis and Haemostasis : JTH·C PuyO J T McCarty
May 23, 2013·Journal of Thrombosis and Haemostasis : JTH·R S WoodruffB A Sullenger
Jul 22, 2014·Journal of Thrombosis and Haemostasis : JTH·R EngelN J Mutch
May 12, 2010·Journal of Thrombosis and Haemostasis : JTH·J Caen, Q Wu
Apr 23, 2014·International Journal of Laboratory Hematology·S de MaatC Maas
Sep 22, 2015·Thrombosis Research·Paola E J van der MeijdenPieter H Reitsma
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·J H Morrissey, S A Smith
Jul 21, 2015·The Journal of Clinical Investigation·Jenny BjörkqvistThomas Renné
Jul 18, 2015·Thrombosis Journal·Hiroshi DeguchiJohn H Griffin
Aug 19, 2011·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Konrad BorkGünther Witzke
May 1, 2016·The Journal of Allergy and Clinical Immunology·Steven de MaatCoen Maas
May 22, 2016·Thrombosis Research·Daria Zamolodchikov, Sidney Strickland

❮ Previous
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Methods Mentioned

BETA
transmission electron microscopy
circular dichroism
ELISA
fluorescence assay
protein assay

Software Mentioned

GraphPad Prism
Graphpad Instat

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