NFκB is an Essential Intermediate in the Activation of Endothelial Cells by Anti-β₂-Glycoprotein 1 Antibodies

Summary

Antiphospholipid antibodies (aPLA) are associated with thrombophilia and recurrent pregnancy loss. They bind directly to anionic phospholipids or via phospholipid-binding proteins such as β₂-glycoprotein 1 (β₂GP1). The underlying mechanisms by which aPLA induce a thrombophilic phenotype are not well understood.

The present work was done to determine whether antibodies to β₂GP1 activate endothelial cells (EC) and whether NFκB is involved in this activation. Incubation of EC with these antibodies resulted in a redistribution of NFκB 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 NFκB abolished the response to these antibodies. In comparison to anti-β₂GP1 antibodies, incubation of EC with TNF resulted in a more rapid (within 30 minutes) redistribution of NFκB 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 NFκB response to anti-β₂GP1 antibodies is indirect.

Taken together our results imply that NFκB is an essential intermediate in the activation of EC by anti-β₂GP1 antibodies.

Keywords

β₂-glycoproteins - endothelial cells - NFκB - adhesion molecules - tissue factor

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