Alterations in chemotactic factor-induced responses of neutrophils and monocytes from chronic dialysis patients

Chronic renal failure patients on dialysis have an increased susceptibility to infection. Previous studies have demonstrated that these patients have a decreased in vitro neutrophil (PMN) chemotactic response and a reduction in C5a receptor availability on both PMN and monocytes. This study was designed to determine if other chemotactic factor-mediated responses of PMN and monocytes from hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) patients are abnormal. The responses investigated included in vitro chemotaxis, superoxide generation, H2O2 production, and myeloperoxidase (MPO) release. These studies showed that PMN from HD and CAPD patients are significantly decreased in their chemotactic response to both C5a and fMLP when compared to normal controls. The response of HD patient's PMN to C5a was decreased by an average of 55.1% (p less than 0.005) and for CAPD patients by 49.7% (p less than 0.01). Similarly, chemotactic responses to fMLP were decreased by an average of 44.7% (p less than 0.005) for HD patients and 36.3% (p less than 0.02) for CAPD patients. Superoxide anion production by PMN and monocytes from HD and CAPD patients in response to C5a and fMLP was also significantly decreased compared to controls. PMN superoxide production in response to C5a was decreased by an average of 36.5% (p less than 0.001) for HD patients and 32.0% (p less than 0.001) for CAPD patients. fMLP-stimulated production of superoxide was also decreased but to a lesser degree with a mean decrease of 18.0% (p less than 0.01) for HD patients and 24.1% decrease (p less than 0.01) for CAPD patients. This decreased responsiveness was restricted to C5a- and fMLP-stimulated superoxide production since phorbol myristate acetate (PMA)-stimulated responses were comparable to controls. A similar pattern of decreased superoxide production was found with monocytes from these patients. Comparable decreases in chemotactic factor-stimulated responses were also observed in a flow cytometric assay of H2O2 production in both PMN and monocytes and an in vitro assay of MPO release from PMN. Analysis of the binding of fluorescent C5a to PMN showed a direct correlation between decreased C5a binding and decreased O2- production and MPO release. Since all of these chemotactic factor-stimulated events are involved in the inflammatory process and the killing of microorganisms, alterations in these WBC functions in dialysis patients may contribute to their increased susceptibility to infection.