Efeito das toxinas urêmicas p-cresol e espermidina sobre o mecanismo de apoptose e função de neutrófilos polimorfonucleares (PMN)

• Ano de defesa: 2009
• Autor(a) principal: Carvalho, José Tarcisio Giffoni de [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: CD11b; CD95; Mecanismos de apoptose e estresse oxidativo; Toxinas urêmicas; Apoptosis; Uremia; ROS production; Uremic toxins
• Link de acesso: https://repositorio.unifesp.br/handle/11600/9363

Background: In Chronic Kidney Disease (CKD) patients, bacterial infections are the first cause of hospitalization and the second cause of mortality. PMN isolated from CKD patients display accelerated apoptosis and dysfunction, which may predispose the CKD patients to infections. Some uremic toxins have been associated with PMN dysfunction. In this study, we investigated the effect of spermidine and p-cresol on apoptosis and function on PMN from healthy subjects and PMN from CKD patients. Methods: Using a flow-cytometric we have measured the effect of spermidine and p-cresol on apoptosis, ROS production unstimulated and stimulated (S.aureus and PMA) and expression of CD95, Caspase 3 and CD11b on PMN from healthy subjects and PMN from CKD patients. Results: After incubation with p-cresol and spermidine, we did not observe any changes in apoptosis, viability or expression of caspase 3 and CD95 in PMN from healthy subjects. PMN from healthy subjects incubated for 10 minutes with spermidine demonstrated a significant reduction in spontaneous, S. aureus and PMA-stimulated ROS production. p-cresol induced a decrease in PMAstimulated ROS production. Spermidine and p-cresol also induced a decrease in the expression of CD11b on PMN from healthy subjects. When these toxins were incubated with PMN from CKD patients no changes were observed between the groups regarding all parameters investigated. On the other hand, PMN from CKD patient displayed decreased viability and ROS production, compared to PMN from healthy subjects. Conclusion: spermidine and p-cresol decreased the expression of CD11b and oxidative burst of PMN from healthy subjects and had no effect on PMN apoptosis and viability. PMN from healthy volunteers were more susceptible than PMN from CKD patients to spermidine and p-cresol-induced changes in ROS production and CD11b expression.