Phagocytic release of lysosomal enzymes from guinea pig neutrophils—regulation by corticosteroids, autonomic neurohormones and cyclic nucleotides

Abstract

The effects of various pharmacologic agents on the capacity of guinea pig neutrophils to phagocytize serum-treated zymosan particles and release lysosomal enzymes were determined. Neutrophils (10 7) and zymosan were incubated in Krebs-Ringer phosphate (KRP) medium containing 7.5 mM glucose, pH 7.4, at 37° in the absence and presence of corticosteroids, cyclic nucleotides, and adrenomimetic and cholinomimetic agents. Methylprednisolone hemisuccinate, triamcinolone acetonide, dexamethasone acetate, paramethasone acetate and hydrocortisone hemisuccinate reduced particle uptake by and discharge of lysosomal enzymes from guinea pig neutrophils. Aldosterone hemisuccinate and deoxycorticosterone acetate were inactive. Adrenomimetic (e.g. epinephrine) agents inhibited particle uptake by and lysosomal enzyme secretion from neutrophils, and cholinomimetic (e.g. acetylcholine) agents accelerated lysosomal enzyme release but had no effect on phagocytosis. Cyclic 3',5'-adenosine monophosphate (cyclic AMP) and one of its analogs inhibited particle ingestion by and lysosomal enzyme release from neutrophils; and this inhibition was potentiated by theophylline. Cyclic 3',5'-guanosine monophosphate (cyclic GMP), in contrast to the actions of corticosteroids, adrenomimetic agents and cyclic AMP, accelerated lysosomal enzyme secretion but had no effect on particle uptake. Cyclic GMP did not affect release of cytoplasmic lactate dehydrogenase, thus indicating maintenance of cell viability during release of lysosomal enzymes. Cytochalasin B, an agent which blocked phagocytic uptake of zymosan, did not interfere with inhibition of lysosomal enzyme secretion by corticosteroids, adrenomimetic agents and cyclic AMP or acceleration of this event by cholinomimetic agents or cyclic GMP. These studies indicate that guinea pig neutrophils are capable of releasing lysosomal enzymes during phagocytosis of zymosan and that certain agents can modulate lysosomal enzyme secretion and/or phagocytosis.