Calcium-dependent activation of human neutrophils by a synthetic ionophore

Synthetic block copolymers composed of polyoxyethylene and poly-oxypropylene have been demonstrated to possess ionophore activity selective for monovalent cations and to cause histamine release from mouse mast cells and human basophils. We now report calcium-dependent release of granule contents from human neutrophils by the most active of these agents, TI30R2. At a concentration of 100 micrograms/ml (12.5 microM), net lysozyme release ranged from 17-40% after 30 minutes incubation at 37 degrees. Lysozyme release was dose-dependent over stimulus concentrations of 5-50 micrograms/ml (0.625-6.25 microM). Release was dependent upon the presence of extracellular calcium. T130R2 did not induce the release of superoxide anions over 30 minutes of incubation. As T130R2 induces sodium influx into cells, it is likely that a depolarizing influx of sodium ions in the presence of extracellular calcium constitutes a sufficient signal for granule release but not superoxide production by human neutrophils.