MECHANISMS OF ACTIVATION OF ENDOTHELIAL CELLS BY APA IN VITRO AND IN VIVO

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The present study proposes to examine the mechanism(s) by which pathogenic murine antiphospholipid antibodies (aPL) adhere to endothelial cell (EC) and induce their activation in vitro and in vivo. The in vivo experiments will be done using a unique animal model of microcirculation. By using different monoclonal antibodies we will also examine the nature of the epitope that these antibodies may recognize on the surface of endothelial cells. The specific aims of this project are: 1. To determine whether murine antiphospholipid antibodies with specificity to phospholipids alone (3F4E2), or with specificity to B2GP1 (4C5G2) activate endothelial cells (EC) in vitro. To determine whether this activation is dependent on B2GP1. 2. To establish whether other phospholipid binding proteins such as placental anticoagulant protein I (PAP I) or the viral peptide T ADL from human adenovirus 2, that shares structural homology with the phospholipid binding site of B2GP1, can interact with aPL in the activation of EC. To establish whether these proteins compete with B2GP1 for the activation of EC by aPL. 3. To determine whether EC are activated by aPL antibodies in vivo. This will be determined by measuring the adhesion of leukocytes to EC in a mouse model of microcirculation.