通过调节肾移植患者血小板和淋巴细胞的外核苷酶增加移植物存活

Aline Mânica, Sarah Franco Vieira de Oliveira Maciel, Maiara Vanusa Guedes Ribeiro, A. Paiz, Matheus Ribeiro Bizuti, Margarete Dulce Bagatini, D. T. Resende e Silva
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摘要

背景:尽管长期生存期有限,但肾移植是终末期疾病患者肾脏替代治疗的最佳形式。细胞外嘌呤能信号的组成部分在器官移植相关的炎症和免疫反应中起着重要作用。它们可能是避免移植物排斥反应的替代靶点。材料与方法:分析淋巴细胞和血小板中ATP、ADP和AMP核苷酸的水解情况,并定量测定ATP和ADA活性。我们获得了30例接受肾移植的患者样本,其中15例移植时间少于1年(急性反应),15例移植时间在1 - 3年(慢性反应)。结果:在移植时间为1 - 3年的组中,可以发现血小板中ATP量明显减少,ATP水解增加,AMP水解减少,ADA活性增加,血小板中也是如此。在淋巴细胞样本中,ADA活性显著降低,ATP的数量也显著减少。结论:从本研究获得的数据可以推断,腺苷可以降低促炎细胞因子,提高移植物存活率,降低移植物抗宿主病的强度。ATP信号可以发挥炎症作用并调节嘌呤能信号级联,为抗慢性移植排斥的药物治疗提供了新的途径。
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Increased Graft Survival through Ectonucleotidases Modulation in Platelets and Lymphocytes of Kidney Transplanted Patients
Background: despite limited long-term survival, kidney transplantation is the best form of renal replacement therapy for terminal disease patients. Components of extracellular purinergic signaling plays a fundamental role on inflammation and immune response related to organ transplantation. They could be alternative targets to avoid graft rejection. Materials and Methods: The hydrolysis of ATP, ADP and AMP nucleotides was analyzed in both lymphocytes and platelets, as well as the quantification of ATP and ADA activity. A sample of 30 patients who underwent kidney transplants was obtained, of which 15 had a transplant time of less than one year (acute response) and 15 had a transplant time between one and three years (chronic response). Results: In the group with transplantation time between one and three years, it was possible to identify a significant decrease in the amount of ATP, increase in ATP hydrolysis in platelets, decrease in AMP hydrolysis and increase in ADA activity, also in platelets. In the lymphocyte sample, there was a significant reduction in ADA activity as well as a decrease in the amount of ATP. Conclusions: From the data obtained in the study, it can be inferred that adenosine can reduce pro-inflammatory cytokines, providing greater graft survival and reducing the intensity of graft-versus-host disease. ATP signaling exerts inflammatory effects and modulates the purinergic signaling cascade, offering new avenues for drug therapies to combat chronic graft rejection.
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