Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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Originally published online as doi:10.1189/jlb.0603288 on December 12, 2003

Published online before print December 12, 2003
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(Journal of Leukocyte Biology. 2004;75:495-503.)
© 2004 by Society for Leukocyte Biology

Constitutive and regulated expression of platelet basic protein in human monocytes

Ahmed El-Gedaily, Gabriele Schoedon, Markus Schneemann and Andreas Schaffner1

Department of Medicine, University Hospital, Zürich, Switzerland

1 Correspondence: Department of Medicine AW9, Research Unit Medical Clinic B, University Hospital, CH-8091 Zürich, Switzerland. E-mail: klinsar{at}usz.unizh.ch

Platelet basic protein (PBP) and several of its derivatives are known for their broad range of functions as signaling molecules and cationic antimicrobial peptides and were considered hitherto megakaryocyte- and platelet-specific. In search of glucocorticoid-regulated antimicrobial systems of monocytes, we found a 15-fold down-regulation of PBP mRNA by differential display. Regulation was confirmed in vivo even at low prednisone doses. Quantitative mRNA analyses confirmed down-regulation also for platelets. Western blotting and immunostains showed down-regulation at the protein level. Pro-PBP derivatives were in the size range of 7.5-14 kD and in immunostains, gave granular cytoplasmatic patterns. Interleukin (IL)-4 and IL-10 induced a similar down-regulation. Phagocytosis resulted in an increase of smaller derivatives in the range of 7.5 kD. Stimulation with interferon-{gamma} and lipopolysaccharide did decrease expression of PBP and affected derivatization. Expression of PBP and its derivatives is not restricted to the megakaryocytic cell lineage. PBP and some of its derivatives might contribute to the antimicrobial armamentarium of mononuclear phagocytes or have monokine functions. Our studies define PBPs as one among the many immunosuppressive targets of glucocorticoids.

Key Words: macrophages • antimicrobial cationic peptides • ß-thromboglobulin • glucocorticoids/immunology




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