Complement Activation and Thrombin Generation by MBL Bound to β2-Glycoprotein I.

ABSTRACT: β2-Glycoprotein I (β2-GPI) is an abundant plasma glycoprotein with unknown physiological function and is currently recognized as the main target of antiphospholipid Abs responsible for complement activation and vascular thrombosis in patients with antiphospholipid syndrome (APS). In this study, we provide evidence that mannose-binding lectin (MBL) binds to β2-GPI in Ca⁺⁺ and a dose-dependent manner and that this interaction activates complement and promotes complement-dependent thrombin generation. Surprisingly, a significant binding was observed between MBL and isolated domains II and IV of β2-GPI, whereas the carbohydrate chains, domain I and domain V, were not involved in the interaction, documenting a noncanonical binding mode between MBL and β2-GPI. Importantly, this intera

SUBMITTER: Durigutto P 

PROVIDER: S-EPMC7489996 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature