Chemiluminescence and superoxide anion production by leukocytes from chronic hemodialysis patients.
During phagocytosis or in response to a soluble stimulus, polymorphonuclear leukocytes (PMN) undergo a burst of oxidative metabolism involved intimately in antimicrobial activity. Superoxide anion produced during the burst is bactericidal either directly or as an intermediate metabolite. In addition, stimulated PMN's emit light or chemiluminescence (CL). CL is a sensitive measure of PMN oxidative potential and correlates with antimicrobial activity. Because of the increased susceptibility to infection observed in patients on chronic hemodialysis (CHD), we studied superoxide anion production and luminol-amplified CL in PMN's from CHD patients and in age-matched controls in the resting state and in response to phorbol myristate acetate (PMA). Studies in autologous serum showed higher CL resting values in PMN's from CHD patients, and crossincubation studies indicated that this is a result of factor(s) in the patients' serum. In response to PMA, PMN's from patients on CHD in autologous serum had significantly (P less than 0.05) less of an increase (phorbol-stimulated minus resting values) in CL as compared with controls (peak time values, 60 +/- 5 x 10(3) cpm for patients vs. 76 +/- 5 x 10(3) cpm for controls). With crossincubation studies, these differences persisted, suggesting that there is a defect intrinsic to the patient PMN. Studies done after dialysis showed a significant reduction in resting values. The decreased response to PMA stimulation remained, however. No difference in superoxide anion production (superoxide-dismutase-inhibitable ferricytochrome c reduction) was seen in PMN's from patients on CHD compared with controls. This along with other studies indicating normal nitroblue tetrazolium (NBT) reduction in PMN's from CHD patients indicates that the decreased CL is due to superoxide-anion-independent mechanisms. Because CL correlates well with antimicrobial activity, the reduced response to PMA observed in neutrophils from patients on CHD may explain, at least in part, the increased susceptibility to infection in these patients.
D000328:Adult; D006801:Humans; D007676:Kidney Failure, Chronic / Q000276:immunology*; D008163:Luminescent Measurements; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D006435:Renal Dialysis; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen