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Sylvie Dunoyer-Geindre, Philippe de Moerloose, Batrix Galve-de Rochemonteix, Guido Reber, Egbert K. O. Kruithof
NFB is an Essential Intermediate in the Activation of Endothelial Cells by Anti-2-Glycoprotein 1 Antibodies
Antiphospholipid antibodies (aPLA) are associated with thrombophilia and recurrent pregnancy loss. They bind directly to anionic phospholipids or via phospholipid-binding proteins such as 2-glycoprotein 1 (2GP1). The underlying mechanisms by which aPLA induce a thrombophilic phenotype are not well understood. The present work was done to determine whether antibodies to 2GP1 activate endothelial cells (EC) and whether NFB is involved in this activation. Incubation of EC with these antibodies resulted in a redistribution of NFB from the cytoplasm to the nucleus after a delay of several hours. This was accompanied by an increased expression of tissue factor and of the leukocyte adhesion molecules ICAM-1, VCAM-1 and E-selectin. Inhibition of the nuclear translocation of NFB abolished the response to these antibodies. In comparison to anti-2GP1 antibodies, incubation of EC with TNF resulted in a more rapid (within 30 minutes) redistribution of NFB and a more pronounced expression of tissue factor and of the leukocyte adhesion molecules. The slower response to the antibodies as compared to TNF suggests that the NFB response to anti-2GP1 antibodies is indirect. Taken together our results imply that NFB is an essential intermediate in the activation of EC by anti-2GP1 antibodies.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 88, 11/2002
Pages: 851 - 857