Inhibition of neutrophil function by hydrogen peroxide. Effect of SH-group-containing compounds.
Stimulated neutrophils generate appreciable amounts of hydrogen peroxide (H2O2) which may be responsible for auto-oxidative injury and damage to adjacent cells. In the present study we describe inhibitory effects of H2O2 on neutrophil phagocytosis, bactericidal activity and associated metabolic processes as well as the effect of non-protein SH-compounds on H2O2-treated cells. Preincubation of neutrophils with low concentrations of H2O2 (1 mumoles/5 X 10(6) cell) results in delayed phagocytosis of Escherichia coli, which returns to normal levels in the later stages of incubation, while the activity of the HMPS and the production of O-2 and H2O2 remain unaffected. Bactericidal activity of the cells was more sensitive to peroxide treatment and even at low concentrations H2O2 induced some inhibition (12.2%) of neutrophils' capacity to kill E. coli. Increasing the concentrations of H2O2 in the preincubation mixtures resulted in a progressive decline in the neutrophils phagocytic and killing capacity for E. coli and was accompanied by inhibition of HMPS activity and the release of granule enzymes but not of O-2 or H2O2. The H2O2/O-2 molar ratio of peroxide-treated cells was elevated by up to 26.7% and this was followed closely by the reduction in the intracellular levels of reduced glutathione (GSH). Incubation of H2O2-treated neutrophils with all five SH-compounds used in the study resulted in the improvement of the phagocytic capacity of the cells. Improvement of the bactericidal capacity and degranulation responses of H2O2-treated neutrophils was achieved by incubation with cysteine, penicillamine, alpha-MPG and MMPC but not GSH. Stimulus-dependent H2O2 production by H2O2-treated cells, the H2O2/O-2 molar ratio and the intracellular levels of GSH remained unaltered after treatment with SH-compounds. The data shows that SH-compounds, in addition to their antiinflammatory properties, also have the ability to reverse the oxidant-induced inhibition of neutrophil function, a property of potential therapeutic significance.
D001770:Blood Bactericidal Activity / Q000187:drug effects; D005978:Glutathione / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010427:Pentose Phosphate Pathway; D010587:Phagocytosis / Q000187:drug effects; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D013438:Sulfhydryl Compounds; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D010100:Oxygen