Mechanism of Nucleoside Triphosphate Diphosphohydrolase-1-Associated Imbalance in Adenosine Diphosphate Degradation, B-Cell Activation, and Related Injury During Acute Antibody-Mediated Rejection
Autor: | Wei Huang, Zhigang Li, Yonghong Zhang, Daxue Tian, G. Wei, Xinlu Wang |
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Rok vydání: | 2017 |
Předmět: |
Graft Rejection
Male medicine.medical_specialty Mice Nude Lymphocyte Activation 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Adenosine Triphosphate Antigen Antigens CD Internal medicine medicine Extracellular Animals Platelet Platelet activation RNA Messenger Cell Size Transplantation Messenger RNA B-Lymphocytes Apyrase Skin Transplantation Platelet Activation Adenosine Diphosphate Adenosine diphosphate Endocrinology chemistry Apoptosis 030220 oncology & carcinogenesis Nucleoside triphosphate 030211 gastroenterology & hepatology Surgery |
Zdroj: | Transplantation proceedings. 50(5) |
ISSN: | 1873-2623 |
Popis: | Objective The objective of this study was to investigate the effect of nucleoside triphosphate diphosphohydrolase-1 (NTPDase1) during acute antibody-mediated rejection (AMR). Methods NTPDase1 overexpression, NTPDase1 knockout, and wild-type nude mice skin graft models were used to induce acute AMR. NTPDase1 expression in B cells, NTPDase1 messenger RNA expression in skin grafts, extracellular adenosine diphosphate (ADP) concentration, B-cell volume and surface antigens expression, average platelet transport rate, and ultrastructure and apoptosis of skin graft cells were investigated. Results During acute AMR in nude mice, higher NTPDase1 expression caused lower extracellular ADP concentration, smaller increase in B-cell volume, and major histocompatibility complex II surface antigen expression, suggesting a negative correlation between them; higher NTPDase1 expression also caused slower average platelet transport rate and less severe skin graft injury, suggesting a negative correlation between them. Pretreatment with high-dose exogenous NTPDase1 inhibited platelet activation and protected skin grafts, but it resulted in prolonged bleeding time (by 51.4%) and prolonged coagulation time (by 44.1%). Conclusion An NTPDase1-associated imbalance in extracellular ADP degradation may contribute to B-cell activation, platelet activation, and more severe skin graft injury in nude mice. Pretreatment with high-dose exogenous NTPDase1 effectively protected skin grafts in nude mice at 1 week, but it increased the risk of bleeding. |
Databáze: | OpenAIRE |
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