IngentaConnect Phosphatidylserine Expression on Cell Surfaces Promotes Antibody-...

Authors: Dombroski D.¹; Balasubramanian K.²; Schroit A.J.²

Source: Journal of Autoimmunity, Volume 14, Number 3, May 2000 , pp. 221-229(9)

Abstract:

Beta-2-glycoprotein I ( beta 2GP1) has been implicated as the primary antigenic target in antiphospholipid syndrome. To study the role beta 2GP1 antibodies play in thrombosis associated with this syndrome, the clearance and binding of phosphatidylserine (PS)-containing target membranes were monitored in beta 2GP1-immune mice. Clearance in immune mice (T_1/24.8 min) was faster than in normal mice (T_1/211.0 min). Analysis of PS vesicles recovered from immune mice by sequencing and Western blotting showed the presence of bound beta 2GP1 and autologous antibody, respectively. Bleeding times in immune mice were sim 30% shorter than in control mice. In vitro clotting times, however, were the same in both populations. To determine if the in vivo results could be attributed to the interaction of autoantibodies with the vascular endothelium, the binding of PS-containing target membranes to normal and apoptotic endothelial cells was studied. While endothelial cells bound PS vesicles, beta 2GP1 reduced uptake by sim 50% in both normal and apoptotic endothelium. In the presence of beta 2GP1 antibodies, however, uptake in apoptotic cells, but not normal cells, increased by more than two-fold. These results suggest that thrombosis in antiphospholipid syndrome could, in part, be due to antibody-dependent cross-linking of beta 2GP1 bound to PS-expressing cells and the vascular endothelium. Copyright 2000 Academic Press

Language: English

Document Type: Research article

Affiliations: 1: The University of Texas School of Public Health Houston, Houston, Texas, 77030, U S A 2: The Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, U S A

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Phosphatidylserine Expression on Cell Surfaces Promotes Antibody-dependent Aggregation and Thrombosis in 2-glycoprotein I-immune Mice