Cardiolipin on the surface of apoptotic cells as a possible trigger for antiphospholipid antibodies

This study provides evidence that cardiolipin (CL) molecules are expressed on the surface of apoptotic cells and are recognized by antiphospholipid an tibodies, purified from patients with the antiphospholipid antibody syndrom e (APS). CL expression on cell surface was demonstrated by high performance thin layer chromatography analysis of phospholipids from plasma membrane p urified fractions and by the positive staining with the CL-specific dye non yl-acridine orange. This finding was complemented with the observation that aCL IgG purified from patients with APS bind to the surface of apoptotic c ells. This staining shows a clustered distribution mostly localized on surf ace blebs. Interestingly, CL exposure on the cell surface preceded the DNA fragmentation, as shown by cytofluorimetric analysis. These findings demons trate that exposure of CL molecules on the cell plasma membrane is an early event of the apoptotic cellular program that may represent an in vivo trig ger for the generation of aCL.