Dissimilar interaction of factor VIII with endothelial cells and lipid vesicles during factor X activation
| Autor: | J. A. Van Mourik, P. M. Koster, H.-J. M. Brinkman, Koen Mertens |
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| Rok vydání: | 1997 |
| Předmět: |
Umbilical Veins
Membrane lipids Biochemistry Factor IXa Cell membrane Tissue factor chemistry.chemical_compound Membrane Lipids medicine Humans Platelet Binding site Lipid bilayer Molecular Biology Cells Cultured Factor VIIIa Phospholipids Binding Sites Factor VIII Chemistry Factor X Cell Biology Enzyme Activation medicine.anatomical_structure Liposomes Biophysics Endothelium Vascular Research Article |
| Zdroj: | The Biochemical journal. 323 |
| ISSN: | 0264-6021 |
| Popis: | A localized and regulated cascade of proteolytic events is a prerequisite for normal haemostasis. The activation of factor X by activated factor IX (factor IXa) in the presence of activated factor VIII (factor VIIIa) is essential for the formation of a fibrin clot at sites of vascular injury. We observed sustained activation of factor X on the surface of vascular endothelial cells, whereas, in agreement with others, on synthetic negatively charged phospholipid vesicles and activated blood platelets factor X activation is transient and starts to decline a few minutes after the onset of the reaction. We examined the mechanism responsible for these differences in factor X activation. Procoagulant membrane and solution were analysed separately for the occurrence of factor VIII and its activation fragments. On negatively charged phospholipid vesicles, on dissociation of factor VIIIa, the 67 kDa light-chain fragment remains associated with the lipid membrane. As a result, factor VIII-binding sites remain occupied, and dampening of factor X activation occurs. In contrast, on monolayers of endothelial cells, no residual factor VIIIa fragments associated with the cell membrane were observed. During endothelial-cell-mediated activation of factor X, accumulation of factor VIIIa fragments was observed in the solution phase only. This finding suggests that, on endothelial cells, factor VIII-binding sites remain accessible for further factor VIII binding, guaranteeing sustained activation of factor X. These data demonstrate that the nature of the procoagulant membrane contributes to the regulation of the cofactor activity of factor VIII and thereby affects the progress of factor X activation. |
| Databáze: | OpenAIRE |
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