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

Journal of Leukocyte Biology

Farshid Dayyani¹  Loems Ziegler-Heitbrock¹  Marion Frankenberger²  Timea Berki³  Kai-Uwe Belge⁴  Matthias Mack⁵ 

[1] Institute for Immunology and Division of Immunology, University of Leicester, United Kingdom Institute for Immunology and Institute for Immunology and Division of Immunology, University of Leicester, United Kingdom Division of Immunology, University of Leicester, United Kingdom Institute for Immunology and Division of Immunology, University of Leicester, United KingdomClinical Cooperation Group Aerosols in Medicine, GSF-Institute for Inhalationbiology Neuherberg and Asklepios Fachklinik, Gauting, Germany; Clinical Cooperation Group Aerosols in Medicine, GSF-Institute for Inhalationbiology Neuherberg and Asklepios Fachklinik, Gauting, Germany; 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 Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Hungary; and Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Hungary; and;Institute for Immunology and Institute for Immunology and Institute for Immunology andMedizinische Poliklinik, University of Muenchen, Germany; Medizinische Poliklinik, University of Muenchen, Germany; Medizinische Poliklinik, University of Muenchen, Germany;

关键词: glucocorticoids;    monocyte;    macrophage;    apoptosis;   

DOI  :  10.1189/jlb.1202612

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown