Enhancement of procoagulant activity in stimulated mononuclear blood cells and monocytes by cyclosporine.
At present cyclosporine is the immunosuppressive agent of choice. Although its introduction has led to an improvement in graft and patient survival, an increase in thromboembolic complications has been reported. We have shown previously that exposure to CsA of TPA- and PHA-stimulated monocyte and mononuclear blood cell cultures increased their cellular thromboplastin activity significantly. In this article we report that CsA enhances the synthesis and release of factor VII, as well as the release of thromboplastin, from LPS- and PHA-stimulated monocytes and whole mononuclear cell cultures. The increase in activity of both factors requires de novo protein synthesis. The synthesis and release of thromboplastin and factor VII from the same cells allow efficient formation of their stoichiometric complex, the most potent trigger of blood coagulation known. The enhancement of their synthesis and release by CsA is therefore potentially very important in the pathogenesis of thromboembolic complications.
D001777:Blood Coagulation / Q000187:drug effects*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003524:Cyclosporins / Q000009:adverse effects / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D005167:Factor VII / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D010835:Phytohemagglutinins / Q000494:pharmacology; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000139:chemically induced
D003524:Cyclosporins; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D003609:Dactinomycin; D005167:Factor VII; D013925:Thromboplastin; D003513:Cycloheximide