Lysosomal and cytosolic pH as regulators of exocytosis in mouse macrophages.

Lysosomal secretion in macrophages may be triggered by any agent that causes a rise in lysosomal pH, i.e. lysosomotropic amines, H(+)-ionophores or inhibitors of vacuolar type H(+)-ATPase. Rises in lysosomal pH and secretion are also triggered upon interaction with yeast-derived zymosan particles. The molecular mechanism for this latter lysosomal alkalinization is not known. Lysosomal secretion is also modulated by changes in cytosolic pH, being somewhat enhanced by cytosolic alkalinization and severely inhibited by cytosolic acidification. These effects are not mediated via changes in lysosomal pH. In addition, a critical, permissive effect on the secretory response is exerted by a protein phosphorylation cascade mediated via protein kinase C. Even its basal activity appears to exert a permissive effect, but stimulation by phorbol ester leads to a synergistic increase in lysosomal secretion. Also, the potent inhibition of lysosomal secretion that develops over many hours of exposure to dexamethasone appears to be due to attenuated signalling via protein kinase C and is partly overcome by phorbol ester stimulation.