Details

Autor(en) / Beteiligte

• Grossi, Claudia
• Artusi, Carolina
• Meroni, PierLuigi
• Borghi, Maria Orietta
• Neglia, Laura
• Lonati, Paola Adele
• Oggioni, Marco
• Tedesco, Francesco
• De Simoni, Maria-Grazia
• Fumagalli, Stefano

Titel

β2 glycoprotein I participates in phagocytosis of apoptotic neurons and in vascular injury in experimental brain stroke

Ist Teil von

• Journal of cerebral blood flow and metabolism, 2021-08, Vol.41 (8), p.2038-2053

Ort / Verlag

London, England: SAGE Publications

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Beta-2 Glycoprotein I (β2-GPI) is the main target of anti-phospholipid antibodies (aPL) in the autoimmune anti-phospholipid syndrome, characterized by increased risk of stroke. We here investigated the antibody independent role of β2-GPI after ischemia/reperfusion, modeled in vivo by transient middle cerebral artery occlusion (tMCAo) in male C57Bl/6J mice; in vitro by subjecting immortalized human brain microvascular endothelial cells (ihBMEC) to 16 h hypoxia and 4 h re-oxygenation. ApoH (coding for β2-GPI) was upregulated selectively in the liver at 48 h after tMCAo. At the same time β2-GPI circulating levels increased. β2-GPI was detectable in brain parenchyma and endothelium at all time points after tMCAo. Parenchymal β2-GPI recognized apoptotic neurons (positive for annexin V, C3 and TUNEL) cleared by CD68+ brain macrophages. Hypoxic ihBMEC showed increased release of IL-6, over-expression of thrombomodulin and IL-1α after re-oxygenation with β2-GPI alone. β2-GPI interacted with mannose-binding lectin in mouse plasma and ihBMEC medium, potentially involved in formation of thrombi. We show for the first time that brain ischemia triggers the hepatic production of β2-GPI. β2-GPI is present in the ischemic endothelium, enhancing vascular inflammation, and extravasates binding stressed neurons before their clearance by phagocytosis. Thus β2-GPI may be a new mediator of brain injury following ischemic stroke.