Impairment of Na+/H+ exchange underlies inhibitory effects of Na+‐free media on leukocyte function

Abstract

Inhibition of activation has been reported when neutrophils are suspended in Na⁺‐free media. We considered the possibility that impairment of cellular pH (pH_i) regulation due to elimination of Na⁺/H⁺ exchange underlies this effect. In the absence of Na⁺, the phorbol ester‐induced respiratory burst was partially inhibited and a concomitant cytoplasmic acidification recorded. Using nigericin/K⁺ to clamp pH_i we demonstrated that the acidification accounts for the inhibition of O₂ uptake. Moreover, in Na⁺‐free media, relieving the acidification by means of ionophores restored maximal O₂ consumption. It was concluded that Na⁺ is not directly involved in signal transduction during stimulation. Instead, omission of Na⁺ affects neutrophile activation indirectly, by impairing pH_i regulation.