Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions.

Abstract

The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased by 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased by 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1--1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contrast, secretion of lysozyme was not affected by glucocorticoids or other steroids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Effects were detected within 1--6 h after addition of the glucocorticoids, became maximum by 24 h, and were reversed during a similar time period after removal of the hormones. The extent of inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1--10 nM) similar to those that half-saturated the specific glucocorticoid receptors in these cells. At high concentrations of dexamethasone (100--1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (greater than 95%) than the secretion of elastase (60--80%). Progesterone alone had no effect on secretion, but it blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1--100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone. These data support the regulatory role of glucocorticoids on macrophage functions at physiological concentrations.

Alveolar macrophage replication. One mechanism for the expansion of the mononuclear phagocyte population in the chronically inflamed lung.

“…Glucocorticoid therapy had no demonstrable effect on the proportion of alveolar macrophages actively replicating in the two large patient groups evaluated, IPF and sarcoidosis. This is important in view of the well-documented ability of glucocorticoids to modulate mononuclear phagocyte replication in animals (60)(61)(62). The present study, however, does not exclude an effect of glucocorticoids on human alveolar macrophage replication.…”

Proteoglycan degradation in hemarthrosis: Intraarticular, autologous blood injection in rat knees

“…whereas plasminogen activator is secreted by stimulated macrophages (Unkeless et ,al. 1974) and synoviocytes stimulated by mononuclear supernatants , and its secretion is inhibited by dexamethasone (Werb 1978. Therefore, it is possible that accumulated macrophages and stimulated synovial lining cells are implicated in the degradation of proteoglycans and serine proteinases, in particular, the plasminogen activator may be responsible for the proteoglycan degradation in experimental hemarthrosis.…”

Effects of in vitro corticosteroids on B cell activation, proliferation, and differentiation.

“…Studies done in the mouse suggest that CS modulation of macrophage interleukin-I production with subsequent suppression of interleukin-2 production is an important mechanism in CS-induced suppression of T cell proliferative responses (29,30). In addition, CS-induced modulation of release of monocyte-soluble factors other than interleukin-I is recognized (31) In contrast to the CS-induced suppression of B cell activation and proliferation, B cell differentiation to an Ig-produced state is either unaltered or enhanced by the presence of in vitro CSs depending on the experimental system employed. The effect of in vitro CSs on Ig production is variable depending on a number of experimental parameters (3).…”