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Interaction of Anti-Phospholipid Antibodies With Late Endosomes of Human Endothelial Cells

Galve-de Rochemonteix, Béatrix
Rosnoblet, Corinne
Lindsay, Margaret
Parton, Robert G.
Reber, Guido
De Maistre, Emmanuel
Wahl, Denis
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Published in Arteriosclerosis, Thrombosis, and Vascular Biology. 2000, vol. 20, no. 2, p. 563-574
Abstract Anti-phospholipid antibodies (APLAs) are associated with thrombosis and/or recurrent pregnancy loss. APLAs bind to anionic phospholipids directly or indirectly via a cofactor such as β2-glycoprotein 1 (β2GPI). The lipid target of APLA is not yet established. Recently, we observed that APLAs in vitro can bind lysobisphosphatidic acid (LBPA). The internal membranes of late endosomes are enriched in this phospholipid. The current study was undertaken to determine to what extent binding of APLA to LBPA is correlated with binding to cardiolipin and to β2GPI and to determine whether patient antibodies interact with late endosomes of human umbilical vein endothelial cells (HUVECs) and thus modify the intracellular trafficking of proteins. Binding of patient immunoglobulin G (n=37) to LBPA was correlated significantly with binding to cardiolipin. Although LBPA binding was correlated to a lesser extent with β2GPI binding, we observed that β2GPI binds with high affinity to LBPA. Immunofluorescence studies showed that late endosomes of HUVECs contain LBPA. Patient but not control antibodies recognized late endosomes, but not cardiolipin-rich mitochondria, even when we used antibodies that were immunopurified on cardiolipin. Incubation of HUVECs with patient plasma samples immunoreactive toward LBPA resulted in an accumulation of the antibodies in late endosomes and led to a redistribution of the insulinlike growth factor 2/mannose-6-phosphate receptor from the Golgi apparatus to late endosomes. Our results suggest that LBPA is an important lipid target of APLA in HUVECs. These antibodies are internalized by the cells and accumulate in late endosomes. By modifying the intracellular trafficking of proteins, APLA could contribute to several of the proposed pathogenic mechanisms leading to the antiphospholipid syndrome.
Keywords Anti-phospholipid antibodiesLate endosomesLysobisphosphatidic acidβ2-glycoprotein IHuman endothelial cells
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GALVE-DE ROCHEMONTEIX, Béatrix et al. Interaction of Anti-Phospholipid Antibodies With Late Endosomes of Human Endothelial Cells. In: Arteriosclerosis, Thrombosis, and Vascular Biology, 2000, vol. 20, n° 2, p. 563-574. doi: 10.1161/01.ATV.20.2.563 https://archive-ouverte.unige.ch/unige:82090

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