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

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 co

SUBMITTER: Maas C 

PROVIDER: S-EPMC2518075 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature