Neutrophil apoptosis, phagocytosis and oxidative metabolism in septic patients

Sepse denota a continuidade de um processo de injuria tecidual onde a disfuncao organica multipla representa sua expressao mais grave. Trata-se de uma condicao patologica associada a altas taxas de mortalidade. Diferentes linhagens celulares estao relacionadas a sua fisiopatogenia. Neutrofilos, por exemplo, sao as primeiras celulas da linha de defesa a migrarem para os sitios de inflamacao e/ou infeccao. Suas funcoes primarias incluem fagocitose de bacterias, elaboracao de enzimas oxidativas e nao oxidativas de degradacao, e formacao de fatores quimiotaticos para recrutar outras celulas inflamatorias. O objetivo desse estudo foi avaliar os efeitos da sepse grave e do choque septico na apoptose e na funcao de neutrofilos, sendo esta analisada pela capacidade fagocitica e pelo metabolismo oxidativo. Para tanto, foram incluidos 10 pacientes com quadro clinico e laboratorial de sepse grave ou choque septico com menos de 48 horas de evolucao, classificados de acordo com as definicoes do consenso de 1992 do American College of Chest Physicians / Society of Critical Care Medicine Consensus Conference, internados em Unidade de Terapia Intensiva do Hospital São Paulo, e 10 individuos sadios, maiores de 18 anos, que nao se encontravam em uso de nenhum medicamento, considerados controles. De cada paciente ou voluntario sadio foram coletadas amostras de 10 ml de sangue arterial ou venoso periferico em tubos estereis com 100 U de heparina para realizacao dos ensaios de apoptose, fagocitose e metabolismo oxidativo, utilizando citometria de fluxo...(au)BV UNIFESP: Teses e dissertaçõe

Matrix metalloproteinases and soluble Fas/FasL system as novel regulators of apoptosis in children and young adults on chronic dialysis

The system of membrane receptor Fas and its ligand FasL compose one of the main pathways triggering apoptosis. However, the role of their soluble forms has not been clarified yet. Although sFasL can be converted from the membrane-bound form by matrix metalloproteinases (MMPs), there are no data on relations between sFas/sFasL, MMPs and their tissue inhibitors (TIMPs) in patients on chronic dialysis—neither children nor adults. The aim of our study was to evaluate serum concentrations of sFas, sFasL, and their potential regulators (MMP-2, MMP-7, MMP-9, TIMP-1, TIMP-2), in children and young adults chronically dialyzed. Twenty-two children on automated peritoneal dialysis (APD), 19 patients on hemodialysis (HD) and 30 controls were examined. Serum concentrations of sFas, sFasL, MMPs and TIMPs were assessed by ELISA. Median values of sFas, sFasL, sFas/sFasL ratio, MMP-2, MMP-7, MMP-9, TIMP-1 and TIMP-2 were significantly elevated in all dialyzed patients vs. controls, the highest values being observed in subjects on HD. A single HD session caused the decrease in values of all parameters to the levels below those seen in children on APD. Regression analysis revealed that MMP-7 and TIMP-1 were the best predictors of sFas and sFasL concentrations. Children and young adults on chronic dialysis are prone to sFas/sFasL system dysfunction, more pronounced in patients on hemodialysis. The correlations between sFas/sFasL and examined enzymes suggest that MMPs and TIMPs take part in the regulation of cell death in the pediatric population on chronic dialysis, triggering both anti- (sFas) and pro-apoptotic (sFasL) mechanisms