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

Journal Article · · J. Exp. Med.; (United States)

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 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased 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 to 1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contast, secretion of lysozyme was not affected by glucocorticoids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. 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 to 10 nM) similar to those that half-saturated the specific glucocorticoid receptors. At high concentrations of dexamethasone (100 to 1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (>95%) than the secretion of elastase (60 to 80%).Progesterone alone had no effect on secretion, but 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 to 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.

Research Organization:
Univ. of California, San Francisco
OSTI ID:
5852408
Journal Information:
J. Exp. Med.; (United States), Journal Name: J. Exp. Med.; (United States) Vol. 147; ISSN JEMEA
Country of Publication:
United States
Language:
English

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Related Subjects

550200* -- Biochemistry
551000 -- Physiological Systems
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CELL CULTURES
COLONY FORMATION
CONNECTIVE TISSUE CELLS
CORTICOSTEROIDS
DEXAMETHASONE
ENZYMES
ESTRADIOL
ESTRANES
ESTROGENS
GLUCOCORTICOIDS
GLYCOSYL HYDROLASES
GUINEA PIGS
HORMONES
HYDROCORTISONE
HYDROLASES
HYDROXY COMPOUNDS
INHIBITION
KETONES
LEUKOCYTES
LYSOZYME
MACROPHAGES
MAMMALS
MAN
MICE
MONOCYTES
ORGANIC COMPOUNDS
PHAGOCYTES
PREGNANES
PRIMATES
PROGESTERONE
RABBITS
RODENTS
SECRETION
SOMATIC CELLS
STEROID HORMONES
STEROIDS
VERTEBRATES