Abstract
PMN from patients with CGD ingest and degranulate normally but do not produce superoxide ≥ or H2O2 in response to phagocytic stimuli. They kill streptococci but not staphylococci. CPZ mimics both the metabolic and bactericidal defects found in CGD PMN. Addition of 10-50 μM CPZ results in increasing inhibition of both ≥ and H2O2 production by PMN treated with opsonized zymosan or digitonin (DIG). CPZ both prolongs the lag time for maximal ≥ production and decreases the final linear rate. These effects cannot be reversed by washing the PMN in CPZ-free buffer. CPZ inhibits ZYM or DIG induced hexosemonophosphate shunt (HMP) activity but not resting on methylene blue induced HMP activity. Ingestion of opsonized particles and release of granular enzymes are unaffected by up to 100 μM CPZ. Incubation of PMN with DIG and CPZ results in undetectable NAD(P)H-dependent ≥ production in membrane fragments. CPZ inhibits NAD(P)H-dependent ≥ production in membrane fragments. 50 μM CPZ prevents the killing of staphylococci but not streptococci by human PMN. At 25 μM CPZ there is a delay in the killing of staphylococci. Thus, the metabolic, enzymatic, and bactericidal defects seen in PMN treated in vitro with CPZ are similar to those found in CGD PMN, and determination of site of CPZ attachment to PMN may aid in understanding the molecular basis of this disorder.
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Cohen, H., Chovaniec, M., Ellis, S. et al. 591 BACTERIAL KILLING AND OXIDATIVE METABOLISM IN CHLORPRDMAZINE (CPZ) TREATED POLYMORPHONUCLEAR LEUKOCYTES (PMN): A MODEL FOR CHRONIC GRANULOMATOUS DISEASE. Pediatr Res 12 (Suppl 4), 462 (1978). https://doi.org/10.1203/00006450-197804001-00596
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DOI: https://doi.org/10.1203/00006450-197804001-00596