Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15

Tiziana Musso; Liliana Calosso; Mario Zucca; Maura Millesimo; Daniela Ravarino; Mirella Giovarelli; Fabio Malavasi; Alessandro Negro Ponzi; Ralf Paus; Silvia Bulfone-Paus

doi:10.1182/blood.V93.10.3531.410k32_3531_3539

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Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15

Journal article

Peer reviewed

Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15

Tiziana Musso, Liliana Calosso, Mario Zucca, Maura Millesimo, Daniela Ravarino, Mirella Giovarelli, Fabio Malavasi, Alessandro Negro Ponzi, Ralf Paus and Silvia Bulfone-Paus

Blood, Vol.93(10), pp.3531-3539

1999-05-15

DOI: https://doi.org/10.1182/blood.V93.10.3531.410k32_3531_3539

PMID: 10233906

Abstract

Interleukin-15 (IL-15) is a potent regulator of T-, B-, and natural killer cell proliferation and displays unusually tight controls of secretion. Even though IL-15 mRNA is constitutively expressed in monocytes/macrophages and is upregulated by a variety of stimuli, evidence for IL-15 cytokine secretion is only found exceptionally, eg, conditions of pathological, chronic inflammation. This raises the possibility that monocytes express membrane-bound IL-15 rather than secrete it. The current study explores this hypothesis. We demonstrate here that biologically active IL-15 is indeed detectable in a constitutively expressed, membrane-bound form on normal human monocytes, as well as on monocytic cell lines (MONO-MAC-6, THP-1, and U937), but not on human T or B cells (MT4, M9, C5966, JURKAT, DAUDI, RAJI, and Epstein-Barr virus-immortalized B-cell clones). Furthermore, cell surface-bound IL-15 is upregulated upon interferon-γ stimulation. Interestingly, monocyte/macrophage inhibitory cytokines such as IL-4 and IL-13 fail to downregulate both constitutive and induced cell-surface expression of IL-15. Membrane-bound IL-15 does not elute with acetate buffer or trypsin treatment, suggesting that it is an integral membrane protein and that it is not associated with the IL-15 receptor complex. Finally, membrane-bound IL-15 stimulates T lymphocytes to proliferate in vitro, indicating that it is biologically active. These findings enlist IL-15 in the fairly small family of cytokines for which the presence of a biologically active membrane-bound form has been demonstrated (eg, IL-1, tumor necrosis factor-, and IL-10) and invites the speculation that most of the biological effects of IL-15 under physiological conditions are exerted by the cell surface-bound form.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.6 Immunology; 1.6.127 T Cell Receptor
Web Of Science research areas: Hematology
ESI research areas: Clinical Medicine

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Title: Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15
Creators: Tiziana Musso - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Liliana Calosso - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Mario Zucca - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Maura Millesimo - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Daniela Ravarino - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Mirella Giovarelli - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Fabio Malavasi - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Alessandro Negro Ponzi - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Ralf Paus - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Silvia Bulfone-Paus - 1 From the Department of Public Health and Microbiology, Postgraduate School of Clinical Pathology, Department of Genetics, Biology and Medical Chemistry, and Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; the Institute of Biology and Genetics, University of Ancona, Ancona, Italy; the Department of Dermatology, Charité, Humboldt University, Berlin, Germany; and the Institute for Immunology, University Hospital Benjamin Franklin, Free University Berlin, Berlin, Germany
Publication Details: Blood, Vol.93(10), pp.3531-3539
Academic Unit: Miller School of Medicine; UMMG Dept of Dermatology & Cutaneous Surgery
Language: English
Resource Type: Journal article
PMID: 10233906
Record Identifier: 991031600597702976