Lag period for superoxide anion generation and lysosomal enzyme release from human neutrophils: effects of calcium antagonists and anion channel blockers.

Responses by human neutrophils to stimulation include superoxide anion generation and lysosomal enzyme release. Both of these responses occur after distinct lag periods. The effects of calcium antagonists and anion channel blockers on these lag periods were examined to discern some activation steps mediating the effects of the chemotactic peptide f-Met-Leu-Phe and the calcium ionophore A23187. The intracellular calcium antagonist TMB-8 and the calmodulin inhibitor trifluoperazine both lengthened the lag periods for superoxide anion generation with either stimulus. This effect was dependent on the concentration of antagonist employed. Similar results were obtained for lysosomal enzyme release in response to A23187, as measured by a rapid centrifugation technique. None of the antagonists altered the lag periods for azurophil granule secretion, as monitored by the 9-aminoacridine technique. These results suggest a role for intracellular free calcium and calmodulin-dependent reactions in activation of the superoxide anion generation system in response to either stimulus, and activation of lysosomal enzyme release system in response to A23187.