Glucocorticosteroid inhibition of nonphagocytic discharge of lysosomal enzymes from human neutrophils

Abstract

Glucocorticosteroids and mineralocorticosteroids were tested for their capacity to inhibit the nonphagocytic discharge of two lysosomal enzymes-a cartilage matrixdegrading neutral protease and ,8-glucuronidase-from highly purified human neutrophils. Lysosomal enzyme discharge from neutrophils adherent to nonphagocytizable, immobilized, heat-aggregated IgC was inhibited by the four glucocorticosteroids-methylprednisolone sodium succinate, triamcinolone acetonide hemisuccinate, paramethasone acetate, and hydrocortisone sodium succinate. These glucocorticoids also inhibited zymosan-induced release of @-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 lyso-

In VitroEffect of the Reproductive Hormones on the Oxidative Burst Activity of Polymorphonuclear Leucocytes from Cows: A Flow Cytometric Study

“…However, as in this study, the killing capacity in physiological cortisol treated PMN was not different from control, it can be concluded that although phagocytosis may be enhanced with physiological concentrations of cortisol, the ultimate capability of the PMN to reduce bacterial numbers is not affected. This is in agreement with Smith (1977) and Ignarro (1977), who demonstrated that physiological concentrations of glucocorticoids had no effect on PMN Iysossomal enzyme release in vitro. As viability lost was not observed, the decrease of activity observed on the cortisol incubated cells can not be attributed to an increase of dead cells.…”

Damage to Pseudohyphal Forms of Candida albicans by Neutrophils in the Absence of Serum In Vitro

“…Because microscopic observations indicated that neutrophils degranulated during contact with pseudohyphae, the effects of hydrocortisone were then studied. Besides the well-known association between corticosteroid therapy and invasive candidiasis (4,5), cortisone may inhibit release of lysosomal enzymes from neutrophils (46). Hydrocortisone inhibited damage to Candida pseudohyphae by neutrophils at levels (10-1 ,uM) which may be reached in vivo after pharmacologic doses.…”

Mechanisms of Glucocorticoid Action on Immune Processes

“…This con cept has been challenged by studies demonstrating that neutrophil lyso somes (the original studies were performed on liver lysosomes) are not stablized even by very high concentrations of corticosteroids (105). Other studies on lysosomes have demonstrated that high concentrations of in vitro corticosteroids can inhibit the release of lysosomal enzymes from neutro phils (99,106,107). Again, the relevance of this to the in vivo situation must be raised.…”