The role of calcium in the initiation of superoxide release from alveolar macrophages.
The role of calcium in the release of superoxide anion (O2-) was examined in alveolar macrophages after stimulation with the soluble stimuli: concanavalin A (Con A), N-formyl methionyl phenylalanine (FMP), and the calcium ionophore. A23187. The release of O2- by Con A was unaffected over a wide range of extracellular calcium concentrations (20 microM to 3 mM), whereas increasing the extracellular calcium above 2 mM inhibited FMP-stimulated O2- release. In contrast, A23187 did not stimulate O2- release in calcium-free medium (less than or equal to 30 microM). The addition of EGTA (50 microM) to calcium-free medium had no effect on Con A stimulation of O2- release or FMP-stimulated O2- release. These results suggest that, for the three soluble stimuli, there are different roles for Ca+2 in the activation and transmission of stimulatory signals across the cell membrane. Con A- or FMP-stimulated calcium efflux from calcium-loaded cells in either calcium-free medium or 0.5 mM calcium-containing medium. In calcium-free medium, FMP transiently retarded 45Ca+2 uptake, while in 0.5 mM calcium-containing medium, FMP transiently stimulated 45Ca+2 uptake. For either Con A or FMP, calcium efflux preceded O2- release by 30-45 sec. Quinine, an agent that blocks membrane hyperpolarization in macrophages, completely blocked O2- release by concanavalin A or FMP and inhibited 45CA+2 efflux by 50% or more for both agents. These results support the hypothesis that redistribution of cellular Ca+2 is one of the initial steps leading to the release of O2-.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D003208:Concanavalin A / Q000494:pharmacology; D003593:Cytoplasm / Q000502:physiology; D004151:Dipeptides / Q000494:pharmacology; D005110:Extracellular Space / Q000502:physiology; D006168:Guinea Pigs; D008264:Macrophages / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000166:cytology; D011803:Quinine / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D004151:Dipeptides; D003208:Concanavalin A; D013481:Superoxides; C017330:N-formylmethionylphenylalanine; D011803:Quinine; D010100:Oxygen; D002118:Calcium