Role of stimulated neutrophils from patients with systemic lupus erythematosus in disturbed immunoreactivity, with special reference to increased oxygen intermediates generated by the neutrophils

Abstract

Zymosan-stimulated neutrophils from 6 patients with untreated, active systemic lupus erythematosus (SLE), from patients with bacterial infections, and from healthy controls, were studied for production of oxygen intermediates (O-2, H2O2, OH . and chemiluminescence) and lysosomal enzymes. Oxygen intermediate production was highest in neutrophils from active SLE patients, while lysosomal enzyme release was highest in neutrophils from patients with bacterial infections. SLE neutrophils, upon culture with autologous or normal lymphocytes, markedly reduced the number of surviving OKT4+ cells and the proliferative response of the surviving cells to mitogens; a reduction was also observed amongst the surviving lymphocytes in the proportion of total T cells and OKT8+ cells, and in the generation of Con A induced suppressor activity. When superoxide dismutase and catalase were included in the neutrophil-lymphocyte co-cultures, the number of T- and OKT8+ cells, and the suppressor activity were restored but not completely (60-75%), the lymphocyte mitogenic response and number of OKT4+ cells were less well restored (40-50%). When lymphocytes were co-cultured with neutrophils from healthy or infected subjects, there was a mild decrease in mitogenic responses and OKT4+ cells, while the suppressor T-cell activity was markedly enhanced. These results were not affected by scavengers. These results suggest that in SLE, reduced T-lymphocyte subpopulations and altered immunoreactivity may be partially due to excessive production of oxygen intermediates and probably other factors by stimulated neutrophils; these results further suggest that in all the subjects, diseased or healthy, neutrophils generate unidentified factors other than oxygen intermediates that reduce the generation of OKT4+ cells and lymphocyte mitogenic responses, and that potentiate suppressor T-cell activity.