Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1202612 on May 22, 2003

Published online before print May 22, 2003
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(Journal of Leukocyte Biology. 2003;74:33-39.)
© 2003 by Society for Leukocyte Biology

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

Farshid Dayyani*,{dagger}, Kai-Uwe Belge*, Marion Frankenberger{ddagger}, Matthias Mack§, Timea Berki and Loems Ziegler-Heitbrock*,{dagger}

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

Correspondence: Professor Loems Ziegler-Heitbrock, Division of Immunology, University of Leicester, Medical Sciences Building, Leicester LE1 9HN, UK. E-mail: lzh1{at}le.ac.uk

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-1ß 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.

Key Words: glucocorticoids • monocyte • macrophage • apoptosis




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