Formyl peptide stimulation of superoxide anion release from lung macrophages: Sodium and potassium involvement

We examined the role of the monovalent cations Na + and K + in the events encompassing the release of O   2 −by alveolar macrophages after stimulation with formyl methionyl phenylalanine (FMP). This was accomplished by determining the effect of changing the extracellular [Na + ] and/or [K + ] on FMP‐stimulated O   2 −production; and measuring 22 Na + 42 K + and 86 Rb + influx and efflux and intracellular [K + ] for control and FMP‐stimulated alveolar macrophages. Stimulated O   2 −production was relatively insensitive to changes in extracellular K + or Na + concentrations until the [Na + ] was decreased below 35 mM. At 4 mM [Na + ], the rate of O   2 −production remained at 75% of the maximal rate observed at physiological concentrations of [Na + ]. Both influx and efflux of 22 Na + were stimulated above control rates by FMP. The increased rates of fluxes lasted for a few minutes suggesting a transient increase in membrane permeability to Na + . Ouabain partially inhibited 22 Na + efflux but had no effect on O   2 −release. The influx of 86 Rb + and 42 K + was not altered by the addition of FMP but was virtually abolished in the presence of 10 μM ouabain or 1 mM quinine. In the presence of extracellular calcium, FMP‐stimulated a prolonged (> 20 minutes) increase in 86 Rb + or 42 K + efflux which was inhibitable by 1 mM quinine. In the absence of extracellular calcium, FMP stimulation of K + efflux was greatly diminished and was not affected by quinine, although quinine still inhibited O   2 −production under these conditions. It was also observed that there was a loss of intracellular K + when cells were stimulated by FMP in the presence of Ca +2 , but not in the absence of Ca +2 . Taken together, these results suggest a minimal direct role, if any, for K + in the events that lead to FMP‐stimulated O   2 −release by alveolar macrophages.