Glucocorticoid receptors and glucocorticoid-sensitive secretion of neutral proteinases in a macrophage line
A continuous line of mouse macrophages (P388D1) has been shown to secrete elastase, collagenase, and plasminogen activator at activities comparable to those of macrophages elicited by an inflammatory stimulus in vivo. At physiologic concentrations anti-inflammatory glucocorticoids selectively and reversibly inhibited secretion of the three proteinases but did not inhibit secretion of lysozyme, a constitutive enzyme produced by the P388D1 cells. The secretion of the neutral proteinases was inhibited 50% by 2 to 10 nM dexamethasone. Proliferation of the macrophages was also glucocorticoid sensitive. The P388D1 macrophages contained about 4000 saturable glucocorticoid-binding sites per cell. Concentrations of hormone saturating the high affinity receptor site (for dexamethasone the dissociation constant for steroid-receptor binding, K/sub d/, was 4 nM) correlated well with concentrations inhibiting secretion of the proteinases. Only glucocorticoids and progesterone competed for binding to the specific receptors. Temperature-sensitive translocation of hormone-receptor complexes from cytoplasm to nucleus similar to that found with rat thymocytes was demonstrated. Thus, the interaction between glucocorticoids and the P388D1 cell line provides a model for the regulation of macrophage secretion of neutral proteinases under normal and stress conditions.
- Research Organization:
- Dartmouth Medical School, Hanover, NH
- OSTI ID:
- 6817765
- Journal Information:
- J. Immunol.; (United States), Journal Name: J. Immunol.; (United States) Vol. 121:1; ISSN JOIMA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL MODELS
CELL CULTURES
CELL PROLIFERATION
CONNECTIVE TISSUE CELLS
CORTICOSTEROIDS
ENZYMES
GLUCOCORTICOIDS
GLYCOSYL HYDROLASES
HORMONES
HYDROLASES
HYDROXY COMPOUNDS
INHIBITION
ISOTOPE APPLICATIONS
KETONES
KINETICS
LABELLED COMPOUNDS
LYSOZYME
MACROPHAGES
MAMMALS
MICE
ORGANIC COMPOUNDS
PEPTIDE HYDROLASES
PHAGOCYTES
PREGNANES
REACTION KINETICS
RECEPTORS
RODENTS
SECRETION
SOMATIC CELLS
STEROID HORMONES
STEROIDS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES