Anti-ß2GPI/ß2GPI induces neutrophil extracellular traps formation to promote thrombogenesis via the TLR4/MyD88/MAPKs axis activation.
Neuropharmacology
; 138: 140-150, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-29883691
ABSTRACT
Antiphospholipid antibodies (aPLs) are a large group of heterogeneous antibodies that bind to anionic phospholipids alone or in combination with phospholipid binding proteins. Increasing evidence has converged to indicate that aPLs especially anti-ß2 glycoprotein I antibody (anti-ß2GPI) correlate with stroke severity and outcome. Though studies have shown that aPLs promote thrombus formation in a neutrophil-dependent way, the underlying mechanisms remain largely unknown. In the present study, we investigated the effect of anti-ß2GPI in complex with ß2GPI (anti-ß2GPI/ß2GPI) on neutrophil extracellular traps (NETs) formation and thrombus generation in vitro and in vivo. We found that anti-ß2GPI/ß2GPI immune complex induced NETs formation in a time- and concentration-dependent manner. This effect was mediated by its interaction with TLR4 and the production of ROS. We demonstrated that MyD88-IRAKs-MAPKs, an intracellular signaling pathway, was involved in anti-ß2GPI/ß2GPI-induced NETs formation. We also presented evidence that tissue factor was expressed on anti-ß2GPI/ß2GPI-induced NETs, and NETs could promote platelet aggregation in vitro. In addition, we identified that anti-ß2GPI/ß2GPI-induced NETs enhanced thrombus formation in vivo, and this effect was counteracted by using DNase I. Our data suggest that anti-ß2GPI/ß2GPI induces NETs formation to promote thrombogenesis via the TLR4/MyD88/MAPKs axis activation, and could be a potentially novel target for aPLs related ischemic stroke.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Thrombosis
/
Beta 2-Glycoprotein I
/
Extracellular Traps
/
Antigen-Antibody Complex
Type of study:
Prognostic_studies
Limits:
Adult
/
Female
/
Humans
/
Male
Language:
En
Year:
2018
Type:
Article