Mechanism of glucocorticoid-induced depletion of human CD14+CD16+ monocytes.
Healthy donors infused with high doses of glucocorticoids [GCs; methyl-prednisolone (MP); 500 mg/day for 3 days] suffer a selective depletion of the CD14(+)CD16(+) monocytes such that these cells are reduced by 95% on day 5. In vitro studies revealed that at 11 h of culture in the presence of 10(-)(5) M MP, no depletion was observed as yet, but a reduction by 80% was seen after 24 h. In dose-response analysis, MP still led to a 50% reduction of CD14(+)CD16(+) monocytes at 10(-)(7) M. Depletion could not be overcome by addition of the cytokines interleukin-1beta or macrophage-colony stimulating factor, and it was independent of CD95. Depletion was, however, inhibited by the caspase 3,8 blocker z-Val-Ala-Asp, suggesting that cell death occurs in a caspase-dependent manner. Furthermore, blockade of depletion by RU-486 indicates that the intracellular GC receptor (GCR) is involved. Measurement of GCR by flow cytometry revealed a 50% higher level of expression in the CD14(+)CD16(+) monocytes. Our studies show a selective depletion of CD14(+)CD16(+) monocytes by GC treatment in vivo and in vitro, an effect to which the modestly increased level of GCR may contribute.
Dayyani
Farshid
F
Institute for Immunology and. Medizinische Poliklinik, University of Muenchen, Germany.
Belge
Kai-Uwe
KU
Frankenberger
Marion
M
Mack
Matthias
M
Berki
Timea
T
Ziegler-Heitbrock
Loems
L
D017209:Apoptosis / Q000187:drug effects*; D061945:Caspase Inhibitors; D018929:Cell Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000502:physiology; D017452:Receptors, IgG / Q000032:analysis
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D018950:Lipopolysaccharide Receptors; D011965:Receptors, Glucocorticoid; D017452:Receptors, IgG