A complement-mediated rat xenotransfusion model of platelet refractoriness
Autor: | Adrianne I. Enos, Kenji M. Cunnion, Pamela S. Hair, Neel K. Krishna |
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Rok vydání: | 2020 |
Předmět: |
Blood Platelets
Male 0301 basic medicine Transplantation Heterologous Immunology 03 medical and health sciences Classical complement pathway Complement inhibitor 0302 clinical medicine Isoantibodies Animals Humans Platelet Complement Pathway Classical Rats Wistar Complement Activation Molecular Biology Opsonin biology Chemistry Rats Complement system Antibody opsonization Disease Models Animal 030104 developmental biology biology.protein iC3b Antibody 030215 immunology |
Zdroj: | Molecular Immunology. 124:9-17 |
ISSN: | 0161-5890 |
Popis: | Background Platelet refractoriness remains a challenging clinical dilemma although significant advancements have been made in identifying human leukocyte antigen (HLA) matched or HLA compatible units. Antiplatelet antibodies are the major risk factor for immune-mediated platelet refractoriness, yet the role of antibody-initiated complement-mediated platelet destruction remains poorly understood. Study Design and Methods Human complement-mediated opsonization and killing of platelets was assayed ex vivo using antibody-sensitized human platelets incubated with complement-sufficient human sera. A new animal model of platelet refractoriness utilizing Wistar rats transfused with human platelets is described. Results Human platelets sensitized with anti-platelet antibodies were rapidly opsonized with iC3b upon incubation in human sera. This opsonization could be completely blocked with a classical pathway complement inhibitor, PA-dPEG24. Complement activation decreased platelet viability, which was also reversible with complement inhibitor PA-dPEG24. A new rat model of platelet refractoriness was developed that demonstrated some platelet removal from the blood stream was complement mediated. Conclusions Complement activation initiated by anti-platelet antibodies leads to complement opsonization and decreased platelet viability. A new rat model of platelet refractoriness was developed that adds a new tool for elucidating the mechanisms of platelet refractoriness. |
Databáze: | OpenAIRE |
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