Superoxide radical production after phorbol ester stimulation in neutrophils of aged donors

Superoxide anion radical production was studied in purified neutrophils of young and old donors after stimulation with phorbol 12-myristate 13-acetate to determine whether phorbol-stimulated activation of NADPH-oxidase was altered by aging. Superoxide radical production of neutrophils of healthy ambulatory elderly (mean age 73 years) was increased compared to young adult controls. Expressed as nmol superoxide/min/mg protein, however, old cells were no different from young. Neutrophils of the elderly contained nearly 20% more protein/cell than young cells, yet neutrophil diameter and volume were not increased in the old cells. Binding affinity and maximum binding capacity of 3H-phorbol 12,13-dibutyrate were similar in young and old neutrophils. Maximum binding capacity was similar whether expressed on a per cell or per mg protein basis. Although others have suggested that initial plasma membrane events leading to superoxide radical production are diminished in aging cells, these studies show that intracellular phases of the mechanisms leading to superoxide radical production are maintained. Superoxide production rate per cell is increased in older persons, associated with a higher protein content per cell but not larger cell size.