Glucocorticoid receptors and cortico-sensitivity in a human clonal monocytic cell line, CM-SM.
CM-SM is a clonal line of human precursor mononuclear phagocytes inducible to macrophage differentiation in response to the tumor promoter phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Untreated CM-SM cells contain single class, high-affinity (KD = 4.0 X 10(-9) M) glucocorticoid-specific receptor sites (approximately 60,000 per cell), as measured by a whole cell assay, at 37 degrees C, using [3H]triamcinolone acetonide (TA). Exposure of CM-SM to dexamethasone (DEX) produced a progressive, dose- and time-related series of changes in CM-SM cell growth, saturation density, morphology, and functional properties, with half-maximal effects at about 10(-9) M for DEX. TA-receptor sites rapidly decreased (about 70%) after DEX treatment, without any apparent change in steroid specificity and affinity. After 5 days in culture with a saturating concentration (3.6 X 10(-8) M) of hormone, the cells reached a saturation density of about 9.0 X 10(6) viable cells/ml (about 4.0 X 10(6) viable cells/ml in the controls), while the modal volume of the resulting cell population was approximately 60%, as compared to the volume of untreated cells. DEX-treated cells appeared less differentiated than controls, as assessed by combined morphologic, antigenic, and cytoenzymatic analyses. DEX almost completely inhibited TPA activation of the following macrophage functions: adherency to the culture plate, expression of lysosomal enzymes, Fc and C3 receptors, and stimulation of phagocytosis. After removal of DEX, the cells, within a few passages, returned to a state apparently identical to the untreated controls and could be induced to macrophage differentiation in response to TPA.
D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects; D003907:Dexamethasone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009000:Monocytes / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*; D013997:Time Factors; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D010703:Phorbol Esters; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D014222:Triamcinolone Acetonide