Antiphospholipid (aPL) antibodies promote the release of plasma membrane-derived vesicles which inhibit the phagocytosis of apoptotic cells - role in Systemic Lupus Erythematosus (SLE) (135.9)

Abstract

Abstract Plasma Membrane-derived Vesicles (PMVs) are membrane-coated vesicles of diameter 0.1 to 1 µm, carrying various proteins inherent in their parental cells. PMVs are released when cells undergo activation/apoptosis via blebbing and shedding. Exposition of phosphotidylserine (PS) on the outer membrane leaflet could explain a role for PMVs in phagocytosis and thrombosis. Increased PMV release, although controlled, is a sign of cellular dysfunction and indicator of cell injury or stress. Patients with inflammatory disease such as Systemic Lupus Erythematosus (SLE) show increased PMV levels in plasma, accompanied by persistent apoptosis and defective clearance which correlates with disease activity. Although still unclear, impaired clearance of apoptotic cells (ACs) may represent a mechanism for the development or enhancement of SLE. Both PMVs and ACs express PS on the outer leaflet of the lipid bilayer as a marker for phagocytosis. We found that PMVs dose dependently inhibit the phagocytosis of ACs by competing for the PS receptor on macrophages. Phosphotidylserine is directly involved as annexin V-labelled PMVs reversed the PMV-mediated inhibition of phagocytosis. We further confirmed elevated PMV levels in SLE patient plasma and showed that the aPL antibodies from the plasma of such patients induced the release of PMVs. These findings show that PMVs can modulate phagocytosis of ACs and suggest an alternative mechanism for PMV enhancement of inflammatory responses.