The role of intracellular acidification in calcium mobilization in human neutrophils

Propionic acid induces a calcium mobilization in human neutrophils which is prevented by pretreatment with phorbol ester or pertussis toxin. The effect is reminiscent of that of chemotactic factors and leukotriene B4 and was attributed to cytoplasmic acidification (Naccache, P.H. et al. (1988) J. Cell. Physiol. 136, 118-124). We show there that other weak acids also induced cytoplasmic alkalinization and calcium mobilization. However, addition of trimethylamine together with propionic acid prevented the cytoplasmic acidification without modifying the calcium mobilization. Propionic acid increased the production of inositol phosphates but this effect was largely prevented by the joint addition of trimethylamine. The ionophores nigericin and monensin can both be forced to produce either cytoplasmic acidification or alkalinization by manipulating the extracellular concentrations of Na+, K+ or H+. Both ionophores produced calcium mobilization in all the cases, irrespective of the direction of the cytoplasmic pH shift. The ionophores were documented to collapse existing pH gradients among the cytoplasm and intracellular compartments. We conclude that the calcium-mobilizing effect of propionic acid and other weak acids is not due to the acidification of the cytoplasm. Our results are consistent, however, with calcium mobilization induced by weak acids and ionophores arising from acidification of an alkaline intracellular compartment.