Glucocorticosteroid inhibition of nonphagocytic discharge of lysosomal enzymes from human neutrophils.
Glucocorticosteroids and mineralocorticosteroids were tested for their capacity to inhibit the nonphagocytic discharge of two lysosomal enzymes--a cartilage matrix-degrading neutral protease and beta-glucuronidase--from highly purified human neutrophils. Lysosomal enzyme discharge from neutrophils adherent to nonphagocytizable, immobilized, heat-aggregated IgG was inhibited by the four glucocorticosteroids--methylprednisolone sodium succinate, triamcinolone acetonide hemisuccinate, para methasone acetate, and hydrocortisone sodium succinate. These glucocorticoids also inhibited zymosan-induced release of beta-glucuronidase from neutrophils that had been pretreated with cytochalasin B in order to completely prevent the onset of phagocytosis. Inhibition by the glucocorticoids of lysosomal enzyme discharge provoked by a soluble divalent cation ionophore was also observed. Neither desoxycorticosterone acetate nor aldosterone hemisuccinate, two mineralocorticosteroids, inhibited lysosomal enzyme release. Similarly, the salt moieties of some of the steroids tested, such as sodium succinate and sodium acetate, failed to elicit an effect on enzyme release. Therefore interference with lysosomal enzyme discharge was restricted to the glucocorticosteroid ring structure. Because interference either with the adherence of neutrophils to immune reactants or with the activities of the discharged lysosomal enzymes by the glucocorticoids could be interpreted as inhibition of lysosomal enzyme release, steroidal effects on these parameters were examined. None of the glucocorticoids tested elicited any significant effects on neutrophil adherence or lysosomal enzyme activity. Thus it appears that glucocorticosteroids are capable of inhibiting directly the nonphagocytic discharge of lysosomal enzymes from human neutrophils.
D000450:Aldosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000494:pharmacology*; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007104:Immune Adherence Reaction; D008247:Lysosomes / Q000201:enzymology*; D008775:Methylprednisolone / Q000494:pharmacology; D008901:Mineralocorticoids / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D010248:Paramethasone / Q000494:pharmacology; D010587:Phagocytosis / Q000187:drug effects; D011480:Protease Inhibitors; D014222:Triamcinolone Acetonide / Q000494:pharmacology
D005938:Glucocorticoids; D008901:Mineralocorticoids; D011480:Protease Inhibitors; D003900:Desoxycorticosterone; D000450:Aldosterone; D005966:Glucuronidase; D014222:Triamcinolone Acetonide; D010248:Paramethasone; D006854:Hydrocortisone; D008775:Methylprednisolone