Role of complement and platelet-activating factor in the stimulation of phagocytosis and reactive oxygen species production during haemodialysis

Background. Neutrophil phagocytic functions have been studied extensively i n haemodialysis (HD) patients; however, results are contradictory and the m echanisms that modulate phagocytosis and oxidative burst during dialysis ar e not completely understood. Methods. The present study investigated neutrophil functions in a selected population of patients before and during clinical dialysis with cuprophane, and polyacrylonitrile (AN69) membranes. We measured phagocytosis of Escher ichia coli and intracellular hydrogen peroxide (H2O2) production by flow cy tometry in whole blood. Results. Before dialysis. neutrophils from HD patients showed normal phagoc ytic capability and H2O2 formation. Phagocytosis of FITC-E. coli was signif icantly stimulated in cuprophane but not AN69-treated patients. Spontaneous and stimulated H2O2 production was enhanced with both cuprophane and AN69 membranes. We then investigated in vitro the role of complement and platele t-activating factor (PAF) in the activation of neutrophils. Incubation of w hole blood with C5a increased phagocytosis but not H2O2 production. On the contrary, the addition of synthetic PAF showed a markedly stimulated H2O2 p roduction without increase in phagocytosis. Moreover, during dialysis with formaldehyde-reused cuprophane, complement activation was abolished and pha gocytosis was no longer enhanced, while the stimulation of H2O2 production persisted. In addition, we also excluded a particular role of the membrane itself in the activation of neutrophils. Conclusion. We demonstrated that in a selected population of HD patients, n eutrophils exhibit normal phagocytic capability and normal intracellular H2 O2 production. During dialysis, the stimulation of phagocytosis observed wi th cuprophane is complement dependent. whereas the enhanced H2O2 production observed with both cuprophane and AN69 membranes might be related to PAF p roduction.