Localization of beta(2)-glycoprotein 1 in late endosomes of human endothelial cells

Antiphospholipid antibodies (APLA) an associated with thrombophilia and rec urrent pregnancy loss. Different mechanisms have been proposed to explain t heir pathogenic effects and among them, we have previously shown that APLA accumulate in late endosomes of human umbilical vein endothelial cells (HUV EC) leading to a redistribution of the cation-independent mannose-6-phospha te receptor (CI-M6PR). Because many APLA are directed towards beta (2)-glyc oprotein 1 (beta (2)GP1)phospholipid complexes, we investigated the localis ation of beta (2)GP1 in HUVEC. By immunofluorescence analysis, using monocl onal and polyclonal anti-beta (2)GP1 antibodies, we detected beta (2)GP1 at the cell surface and in late endosomes. Incubation of HUVEC with anti-beta (2)GP1 antibodies resulted in antibody accumulation at the cell surface an d within late endosomes and in a redistribution of the CI-M6PR from the Gol gi apparatus to late endosomes. The anti-beta (2)GP1 antibodies remained de tectable in late endosomes even after several days of incubation in antibod y-free medium. The accumulation of anti-beta (2)GP1 antibodies in late endo somes of endothelial cells and the resulting modification of intracellular protein trafficking may contribute to the pathogenic effects of these antib odies.