Role of extracellular calcium in neutrophil responsiveness to chemotactic tripeptides

Cellular stores of Ca2+, but not extracellular Ca2+, are required for effective FMLP stimulation of neutrophil O2- production and degranulation. Neutrophils transferred from Ca2+-containing to Ca2+-free medium gradually lose their responsiveness to FMLP, such that after 40 min in the Ca2+-free environment they have lost 60-70% of their initial responsiveness to FMLP. The loss in responsiveness is reflected both in an increase in lag interval and decrease in velocity of O2-synthesis. The rate of decline in responsiveness to FMLP is greatly accelerated when neutrophils incubated in the presence of A23187 and Ca2+-free medium, while the rate of loss of responsiveness to FMLP is not affected by EGTA but the extent of loss is increased. Gradual recovery of FMLP-induced O2- generation occurs when cells are transferred from Ca2+-free to Ca2+-containing medium. PMA-induced neutrophil O2- generation is not influenced by the presence or absence of extracellular Ca2+. It is our view that the rise or fall of neutrophil responsiveness reflects repletion or depletion of cellular stores of Ca2+ essential for stimulus-effector coupling and that the role of extracellular Ca2+ is subservient to maintenance of these stores.