A defect in the oxidative metabolism of human polymorphonuclear leukocytes that remain in circulation early in hemodialysis

Abstract

Abstract Human granulocytes harvested from uremic volunteers 15 min after the initiation of dialysis (at the nadir of neutropenia) were compared to predialysis controls. These intradialysis cells had a significant defect in peak luminol-enhanced chemiluminescence in response to opsonized zymosan, f-Met-Leu-Phe, and phorbol myristate acetate relative to predialysis control cells from the same patients. This defect could not be explained by a decrease in PMN myeloperoxidase concentration. H2O2 secretion by intradialysis cells (2 patients) was also depressed relative to predialysis controls. The ability to perform an independent function, orientation (polarization), was normal in both pre- and intradialysis cells relative to control. Whereas 125I-labeled formyl peptide binding studies demonstrated identical values for affinity and receptor number for predialysis and normal control cells, intradialysis cells displayed a 27% decrease in receptor number. This decrease in available receptor number. This decrease in available receptors may be related to the decreased chemiluminescence observed in response to f-Met-Leu-Phe. Furthermore, the results are consistent with the hypothesis that a defective PMN population remains in the circulation during the neutropenia of hemodialysis.