Anti-β2 Glycoprotein I Antibodies Prevent the De-activation of Platelets and Sustain their Phagocytic Clearance |
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Authors: | Attilio Bondanza Maria Grazia Sabbadini Fabio Pellegatta Valrie S Zimmermann Angela Tincani Genesio Balestrieri Angelo A Manfredi Patrizia Rovere |
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Institution: | a Clinical Immunology and Rheumatology Unit and Cancer Immunotherapy and Gene Therapy Program, Via Olgettina 60, 20132, Milano, Italy;b Department of Cardiology, H San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milano, Italy;c Clinical Immunology, Spedali Civili, Brescia, Italy |
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Abstract: | Exposure to phosphatidylserine (PS) tags dying and senescent cells for removal and identifies activated platelets. In this study we followed the fate of PS-exposing platelets in the presence of antibodies purified from Systemic Lupus Erythematosus (SLE) and primary Anti-phospholipid Syndrome (APS) patients' sera by β2GPI affinity chromatography. Thrombin-activated platelets exposed PS and associated to β2GPI. Both events were required for recognition by antibodies. Human monocyte-derived macrophages phagocytosed activated platelets only. Each macrophage internalized an average of 3.16±0.2 platelets after 60 min at 37°C. Phagocytosis did not increase after longer incubations (4.65±0.26 platelets internalized by each macrophage after 300 min). Recognition of platelets by anti-β2GPI antibodies significantly increased phagocytosis (P< 0.01). Upon withdrawal of thrombin, platelets downregulated PS (PS exposure t1/2: 242 min) and the ability to be recognized by macrophages. Purified β2GPI bound to PS-exposing platelets (association t1/2: 250 min). Phosphatidyl serine exposure and β2GPI association had virtually identical kinetics. Antibody binding prolonged the exposure of the β2GPI/PS complex (t1/2: >1200 min). The ability to phagocytose opsonized platelets was accordingly sustained (5.3±0.2 opsonized platelets were internalized by each macrophage after 60 min and 9.4±0.3 after 300 min). Anti-β2GPI antibodies therefore poise activated platelets in a PS-exposing status, preventing the recycling of their function and favoring their phagocytic clearance. |
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Keywords: | anti-β 2 glycoprotein I antibodies phosphatidylserine phagocytosis platelets |
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