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 ²²Na⁺⁴²K⁺ and ⁸⁶Rb⁺ 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 ²²Na⁺ 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 ²²Na⁺ efflux but had no effect on O 2− release. The influx of ⁸⁶Rb⁺ and ⁴²K⁺ 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 ⁸⁶Rb⁺ or ⁴²K⁺ 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.