title: Protein C inhibitor (PCI) binds to phosphatidylserine exposing cells with implications in the phagocytosis of apoptotic cells and activated platelets.
abstract: Protein C Inhibitor (PCI) is a secreted serine protease inhibitor, belonging to the family of serpins. In addition to activated protein C PCI inactivates several other proteases of the coagulation and fibrinolytic systems, suggesting a regulatory role in hemostasis. Glycosaminoglycans and certain negatively charged phospholipids, like phosphatidylserine, bind to PCI and modulate its activity. Phosphatidylerine (PS) is exposed on the surface of apoptotic cells and known as a phagocytosis marker. We hypothesized that PCI might bind to PS exposed on apoptotic cells and thereby influence their removal by phagocytosis. Using Jurkat T-lymphocytes and U937 myeloid cells, we show here that PCI binds to apoptotic cells to a similar extent at the same sites as Annexin V, but in a different manner as compared to live cells (defined spots on ∼10-30% of cells). PCI dose dependently decreased phagocytosis of apoptotic Jurkat cells by U937 macrophages. Moreover, the phagocytosis of PS exposing, activated platelets by human blood derived monocytes declined in the presence of PCI. In U937 cells the expression of PCI as well as the surface binding of PCI increased with time of phorbol ester treatment/macrophage differentiation. The results of this study suggest a role of PCI not only for the function and/or maturation of macrophages, but also as a negative regulator of apoptotic cell and activated platelets removal.
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rieger
authors.affiliation: Department of Physiology, Center for Phsiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Alice
authors.initials: A
authors.lastname: Assinger
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Katrin
authors.initials: K
authors.lastname: Einfinger
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Barbora
authors.initials: B
authors.lastname: Sokolikova
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Margarethe
authors.initials: M
authors.lastname: Geiger
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000502:physiology*; D002166:Camptothecin / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008863:Microspheres; D010587:Phagocytosis / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects; D011137:Polystyrenes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D018046:Protein C Inhibitor / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D010718:Phosphatidylserines; D011137:Polystyrenes; D018046:Protein C Inhibitor; D002166:Camptothecin