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Misfolded proteins ...
Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation
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- Maas, Coen (författare)
- Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, NL-3508 GA Utrecht, Netherlands
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- Govers-Riemslag, Jos W. P. (författare)
- Maastricht Univ, Lab Clin Thrombosis & Haemostasis, Dept Internal Med, Maastricht, Netherlands
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- Bouma, Barend (författare)
- Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, NL-3508 GA Utrecht, Netherlands
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- Schiks, Bettina (författare)
- Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, NL-3508 GA Utrecht, Netherlands
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- Hazenberg, Bouke P. C. (författare)
- Univ Med Ctr Groningen, Dept Rheumatol & Clin Immunol, Groningen, Netherlands
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- Lokhorst, Henk M. (författare)
- Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, NL-3508 GA Utrecht, Netherlands
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- Hammarström, Per (författare)
- Linköpings universitet,Tekniska högskolan,Biokemi
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- ten Cate, Hugo (författare)
- Maastricht Univ, Lab Clin Thrombosis & Haemostasis, Dept Internal Med, Maastricht, Netherlands
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- de Groot, Philip G. (författare)
- Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, NL-3508 GA Utrecht, Netherlands
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- Bouma, Bonno N. (författare)
- Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA
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- Gebbink, Martijn F. B. G. (författare)
- Univ Med Ctr Utrecht, Dept Clin Chem & Hematol, NL-3508 GA Utrecht, Netherlands
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(creator_code:org_t)
- 2008
- 2008
- Engelska.
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 118:9, s. 3208-3218
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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 kallikreinkinin 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 activation by misfolded protein aggregates.
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- TEKNIKVETENSKAP
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Maas, Coen
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Govers-Riemslag, ...
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Bouma, Barend
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Schiks, Bettina
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Hazenberg, Bouke ...
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Lokhorst, Henk M ...
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visa fler...
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Hammarström, Per
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ten Cate, Hugo
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de Groot, Philip ...
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Bouma, Bonno N.
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Gebbink, Martijn ...
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Journal of Clini ...
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Linköpings universitet