Increased Graft Survival through Ectonucleotidases Modulation in Platelets and Lymphocytes of Kidney Transplanted Patients
Aline Mânica
Health Science Department, Community University of the Region of Chapecó (UNOCHAPECÓ), Chapecó, SC, Brazil.
Sarah Franco Vieira de Oliveira Maciel
Biomedical Sciences, Federal University of Fronteira Sul (UFFS), Chapecó, SC, Brazil.
Maiara Vanusa Guedes Ribeiro
Biosciences and Pathophysiology (PBF), From The State University of Maringá (UEM), Maringá, PR, Brazil.
Alessandra Paiz
Federal University of Paraná (UFPR), Curitiba, PR, Brazil.
Matheus Ribeiro Bizuti
Department of Medicine, Federal University of Fronteira Sul (UFFS), Chapecó, SC, Brazil.
Margarete Dulce Bagatini
Biomedical Sciences, Federal University of Fronteira Sul (UFFS), Chapecó, SC, Brazil.
Débora Tavares de Resende e Silva *
Biomedical Sciences, Federal University of Fronteira Sul (UFFS), Chapecó, SC, Brazil.
*Author to whom correspondence should be addressed.
Abstract
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.
Keywords: Kidney transplantation, purinergic molecules, adenosine triphosphate, chronic renal insufficiency