Inactivation of lysosomal enzymes by the respiratory burst of polymorphonuclear leukocytes. Possible involvement of myeloperoxidase-H2O2-halide system.
Lysosomal enzyme release from PMN during phagocytosis was examined in PMN from healthy subjects and patients with CGD. Normal PMN showed increased extracellular enzyme levels and a marked reduction of total (intracellular plus extracellular) enzyme activity after phagocytosis of STZ. In PMN from patients with CGD, a reduction of total enzyme activity was not observed and much more enzyme than normal was released extracellularly. We have examined the effect of the respiratory burst on enzyme activity mostly to loss of released enzymes. PMA-stimulated normal PMN inhibited the enzyme activity in postphagocytosis media from CGD PMN but PMA-stimulated CGD PMN did not. This inhibition by normal PMA-stimulated PMN was protected by the addition of catalase, histidine, and NaN3. Furthermore, these enzymes were inactivated by cell-free, glucose plus glucose oxidase (as a H2O2 generating system) and NaOCI. Histidine had a protective effect on the enzyme inactivation both by glucose plus glucose oxidase and by NaOCI. In contrast, histidine gave a slight increase of extracellular enzyme levels but failed to restore enzyme activity when added to the medium during phagocytosis in normal PMN. These evidences suggest that the inactivation of lysosomal enzymes is mainly due to MPO-H2O2-halide system, resulting in inhibition of lysosomal enzyme release from PMN during phagocytosis.
D004789:Enzyme Activation; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000201:enzymology; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D010100:Oxygen / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D010545:Peroxides / Q000378:metabolism*; D010587:Phagocytosis; D012119:Respiration
D010545:Peroxides; D010544:Peroxidases; D009195:Peroxidase; D010100:Oxygen