The role of calcium in the age-related decline of neutrophil function.

Upon activation by formyl-methionyl-leucyl-phenylalanine (FMLP), either in the presence of absence of cytochalasin B, neutrophils from old subjects generated significantly less superoxide than did neutrophils from the young. This reduction in activity was associated with a significant decrease in the basal cytosolic calcium concentration and a diminished flux of calcium to the cytosol after activation. At all concentrations of FMLP tested, cytosolic calcium remained significantly lower in neutrophils from the old as compared with the young, whereas permeability to extracellular calcium and efflux of calcium from the cell were also significantly diminished. Pretreatment of the cell with the ionophore ionomycin elevated the cytosolic calcium concentration and significantly improved function in old neutrophils. These findings demonstrate that aging results in alterations in neutrophil calcium homeostasis that may play a role in the age-related decline in neutrophil function.