Differential stimulation by oxygen-free-radical-altered immunoglobulin G of the production of superoxide and hydrogen peroxide by human polymorphonuclear leucocytes.

1. The effect of free-radical-altered IgG (monomer and polymer u.v.-irradiated IgG), compared with that of native and heat-aggregated IgG, on the production rate of superoxide anion and hydrogen peroxide by granulocytes (polymorphonuclear leucocytes) from normal blood and granulocytes obtained from the blood and synovial fluid of patients with rheumatoid arthritis was studied. 2. Similar rates of superoxide production by granulocytes from normal blood at rest and in the presence of any form of IgG were found. In contrast, the rate of hydrogen peroxide production could be stimulated in a dose-dependent fashion by monomer or polymer u.v.-irradiated IgG. 3. The stimulatory effect of free-radical-altered IgG on the rate of hydrogen peroxide production did not occur in the presence of 2-deoxyglucose, which deprives the NADPH:O2 oxidoreductase of its substrate NADPH by inhibition of glycolysis and the pentose phosphate pathway. This points to a stimulatory effect on the direct divalent reduction of oxygen without intermediate superoxide production by this enzyme complex. 4. Granulocytes obtained from the blood and synovial fluid of patients with rheumatoid arthritis reacted differently to polymer u.v.-irradiated IgG. In the presence of this stimulus the rate of release of both superoxide and hydrogen peroxide was increased. Furthermore, these granulocytes synthesized superoxide and hydrogen peroxide at a higher rate than did granulocytes from normal blood in the presence of serum-treated zymosan but not in the presence of phorbol myristate acetate. 5. Taken together, these results indicate that the rate of superoxide and hydrogen peroxide production by the granulocyte NADPH:O2 oxidoreductase depends on the pathological condition of the donor and the type of stimulus used.