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Mechanism of glucocorticoid‐induced depletion of human CD14 + CD16 + monocytes
Author(s) -
Dayyani Farshid,
Belge KaiUwe,
Frankenberger Marion,
Mack Matthias,
Berki Timea,
ZieglerHeitbrock Loems
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1202612
Subject(s) - cd14 , cd16 , biology , flow cytometry , endocrinology , monocyte , glucocorticoid receptor , medicine , intracellular , glucocorticoid , ex vivo , in vitro , immunology , microbiology and biotechnology , immune system , biochemistry , cd3 , cd8
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‐1β 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.