Anti-beta2 glycoprotein I antibodies prevent the De-activation of platelets and sustain their phagocytic clearance.
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 beta2GPI affinity chromatography. Thrombin-activated platelets exposed PS and associated to beta2GPI. 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 degrees 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-beta2GPI antibodies significantly increased phagocytosis (P< 0.01). Upon withdrawal of thrombin, platelets downregulated PS (PS exposure t(1/2): 242 min) and the ability to be recognized by macrophages. Purified beta2GPI bound to PS-exposing platelets (association t(1/2): 250 min). Phosphatidyl serine exposure and beta2GPI association had virtually identical kinetics. Antibody binding prolonged the exposure of the beta2GPI/PS complex (t(1/2): >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-beta2GPI antibodies therefore poise activated platelets in a PS-exposing status, preventing the recycling of their function and favoring their phagocytic clearance.
Bondanza
A
A
Clinical Immunology and Rheumatology Unit and Cancer Immunotherapy and Gene Therapy Program, Via Olgettina 60, Milano, 20132, Italy.
Sabbadini
M G
MG
Pellegatta
F
F
Zimmermann
V S
VS
Tincani
A
A
Balestrieri
G
G
Manfredi
A A
AA
Rovere
P
P
D000906:Antibodies / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000494:pharmacology; D015539:Platelet Activation; D013917:Thrombin / Q000494:pharmacology; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D006023:Glycoproteins; D007074:Immunoglobulin G; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I; D013917:Thrombin