Phagocytosis of platelet microvesicles and beta2- glycoprotein I.
The majority of the antiphospholipid antibodies, present in patients with antiphospholipid syndrome, are directed against conformational epitopes in beta2-glycoprotein I. beta2-glycoprotein I is an anionic phospholipid-binding 50-kDa plasma protein whose physiological role is not clear. Here we investigate the role of beta2-glycoprotein I in the phagocytosis of phosphatidylserine-expressing platelet microvesicles and the effect of autoantibodies to beta2-glycoprotein I on this process. We labelled the glycans of beta2-glycoprotein I with BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-hydrazide without affecting its phospholipid binding capacity. BODIPY-beta2-glycoprotein I bound to platelet microvesicles in a concentration-dependent manner and promoted the phagocytosis of platelet microvesicles by THP-1 derived macrophages in vitro at physiological plasma concentrations with a half maximal effect at approximately 10 microg/ml. beta2-glycoprotein I-stimulated phagocytosis was inhibited by annexin A5 and the phosphatidylserine-binding C1C2 fragment of lactadherin. Furthermore, immunoaffinity purified beta2-glycoprotein I-dependent antiphospholipid antibodies from five patients with antiphospholipid syndrome inhibited the phagocytosis in a concentration-dependent manner. These studies suggest that the binding of beta2-glycoprotein I to phosphatidylserine-expressing procoagulant platelet microvesicles may promote their clearance by phagocytosis and autoantibodies to beta2-glycoprotein I may inhibit this process to induce a procoagulant state.
Department of Pathology and Medicine, Michael E DeBakey Veterans Affairs Medical Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Hanan
H
Abdel-Monem
Swapan K
SK
Dasgupta
Anhquyen
A
Le
Anthony
A
Prakasam
Perumal
P
Thiagarajan
D017304:Annexin A5 / Q000378:metabolism; D000954:Antigens, Surface / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000378:metabolism; D001777:Blood Coagulation; D001792:Blood Platelets / Q000276:immunology / Q000378:metabolism*; D001896:Boron Compounds; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000276:immunology / Q000378:metabolism*; D005456:Fluorescent Dyes; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008894:Milk Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D053482:beta 2-Glycoprotein I / Q000378:metabolism*
C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D017304:Annexin A5; D000954:Antigens, Surface; D001323:Autoantibodies; D001896:Boron Compounds; D005456:Fluorescent Dyes; C098942:MFGE8 protein, human; D008894:Milk Proteins; D010446:Peptide Fragments; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I