Lysosomotropic amines modulate neutrophil calcium homeostasis.

Lysosomotropic amines can raise the acidic internal pH of the neutrophil lysosome and inhibit neutrophil function. Because pH and calcium regulation are intimately connected in various types of excitable cells, we studied the effects of several lysosomotropic weak bases on neutrophil calcium homeostasis. Base-treated cells had normal to minimally elevated resting cytosol free calcium, but weak bases produced significant release of calcium from organelles when this release was directly measured in permeabilized cells, even after depletion of inositol-triphosphate-sensitive stores. Collapse of transmembrane pH gradients with monensin similarly released organelle calcium. The initial cytosol calcium response to f-met-leu-phe was enhanced by some of the lysosomotropic amines but the calcium rise was more transient in base-treated cells than in control samples. These findings suggest that existence of an acidic intracellular compartment, such as the lysosome, is important to normal calcium homeostasis in the neutrophil and that pH sensitivity and inositol triphosphate sensitivity may define two pools of releasable organelle calcium. The effect of pH perturbation on calcium homeostasis may partially account for the inhibition of neutrophil function by lysosomotropic amines.