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Published online before print May 22, 2003

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© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1202612

Received for publication December 18, 2002.
Revised March 13, 2003.
Accepted for publication March 14, 2003.

Article

Mechanism of glucocorticoid-induced depletion of human CD14⁺CD16⁺ monocytes

Farshid Dayyani ^*, Kai-Uwe Belge ^*, Marion Frankenberger , Matthias Mack , Timea Berki ^¶, and Loems Ziegler-Heitbrock ^*@

*Institute for Immunology and Medizinische Poliklinik, University of Muenchen, Germany; Clinical Cooperation Group Aerosols in Medicine, GSF-Institute for Inhalationbiology and Asklepios Fachklinik, Gauting, Germany; ^¶Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Hungary; and Division of Immunology, University of Leicester, United Kingdom

^@ To whom correspondence should be addressed. E-mail: lzh1{at}le.ac.uk.

	Abstract

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-1 or macrophage-colony stimulating factor, and it was independent of CD95. Depletion is, 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.

Key Words: glucocorticoids • monocyte • macrophage • apoptosis

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