GUINEA-PIG NEUTROPHIL CALCIUM-DEPENDENT LYSOSOMAL ENZYME SECRETORY PROCESS - INHIBITION BY NONSTEROID ANTI-INFLAMMATORY AGENTS

A selective release of lysosomal granule-associated β-glucuronidase and acid protease, but not cytoplasmic lactate dehydrogenase, occurs during contact between zymosan-treated serum and cytochalasin B-treated neutrophils. The calcium-dependent aspect of this secretory process is demonstrated by the absence of lysosomal enzyme discharge from neutrophils incubated with zymosan-treated serum in calcium-free Krebs-Ringer phosphate medium containing 7.5 mM glucose, pH 7.4, at 37°. The capacity of the divalent cation ionophore, A23187, to induce lysosomal enzyme release also implies a requirement of calcium for secretion to occur. Further, zymosan-treated serum and ionophore-induced release of β-glucuronidase was accompanied by a marked association of 45CaCl2 with neutrophils. Indomethacin, diftalone, naproxen, ketoprofen and suprofen impeded A23187-stimulated extracellular extrusion of lysosomal enzymes from, and 45CaCl2 association with, neutrophils. Acetylsalicylic acid and flazalone were inactive. The inhibitory effects of these nonsteroid anti-inflammatory agents could be reversed by increasing the extracellular calcium ion concentration. The specificity of calcium in reversing the effects of these agents was indicated by the observation that supplementing the incubation medium with magnesium would not attenuate the action of these nonsteroid agents. Therefore, the regulation of the selective secretion of lysosomal enzymes from neutrophils by nonsteroid anti-inflammatory agents may be related to their capacity to modulate the association of calcium with these cells. © 1979.