APOPTOTIC CELL CLEARANCE IN SYSTEMIC LUPUS-ERYTHEMATOSUS - II - ROLE OF BETA(2)-GLYCOPROTEIN-I

Objective. To analyze the contribution of beta(2)-glycoprotein I (beta (2)-GPI) to apoptotic cell recognition by antiphospholipid antibodies (aPL) and macrophages from patients with autoimmune disease. Methods. Phosphatidylserine expression by Jurkat cells undergoing apoptosis upo n CD95 crosslinking or ultraviolet irradiation was verified by confoca l microscopy of cells stained with fluorescein isothiocyanate-labeled annexin V. beta(2)-GPI was purified by heparin/cationic-exchange chrom atography and was biotinylated or used to purify beta(2)-GPI-specific antibodies by affinity chromatography. Binding to apoptotic cells was assessed by now cytometry. The clearance of H-3-labeled, apoptotic cel ls by macrophages was assessed by beta counting. Results. The array of epitopes generated by beta(2)-GPI association with apoptotic cells sp ecifically targets their recognition and is required for their opsoniz ation by human aPL. Nevertheless, beta(2)-GPI is not required for apop totic cell clearance by human macrophages in the absence of aPL. Concl usion. The proinflammatory clearance of aPL-opsonized apoptotic cells, but not the nonphlogistic clearance of apoptotic cells by scavenger m acrophages, depends on beta(2)-GPI.