Localization of beta2-glycoprotein 1 in late endosomes of human endothelial cells.
Antiphospholipid antibodies (APLA) are associated with thrombophilia and recurrent pregnancy loss. Different mechanisms have been proposed to explain their pathogenic effects and among them, we have previously shown that APLA accumulate in late endosomes of human umbilical vein endothelial cells (HUVEC) leading to a redistribution of the cation-independent mannose-6-phosphate receptor (CI-M6PR). Because many APLA are directed towards beta2-glycoprotein 1 (beta2GP1)phospholipid complexes, we investigated the localisation of beta2GP1 in HUVEC. By immunofluorescence analysis, using monoclonal and polyclonal anti-beta2GP1 antibodies, we detected beta2GP1 at the cell surface and in late endosomes. Incubation of HUVEC with anti-beta2GP1 antibodies resulted in antibody accumulation at the cell surface and within late endosomes and in a redistribution of the CI-M6PR from the Golgi apparatus to late endosomes. The anti-beta2GP1 antibodies remained detectable in late endosomes even after several days of incubation in antibody-free medium. The accumulation of anti-beta2GP1 antibodies in late endosomes of endothelial cells and the resulting modification of intracellular protein trafficking may contribute to the pathogenic effects of these antibodies.
Dunoyer-Geindre
S
S
Division of Angiology and Haemostasis, University Hospital of Geneva, Switzerland.
Kruithof
E K
EK
Galve-de Rochemonteix
B
B
Rosnoblet
C
C
Gruenberg
J
J
Reber
G
G
de Moerloose
P
P
D000906:Antibodies / Q000378:metabolism / Q000494:pharmacology; D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants / Q000276:immunology / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000209:etiology; D011992:Endosomes / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000648:ultrastructure; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D017527:Receptor, IGF Type 2 / Q000187:drug effects / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D006023:Glycoproteins; D017527:Receptor, IGF Type 2; D053482:beta 2-Glycoprotein I