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-α, 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3531-3539 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 93 |
| Issue number | 10 |
| State | Published - May 15 1999 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Biochemistry
- Hematology
- Cell Biology
Cite this
Human monocytes constitutively express membrane-bound, biologically active, and interferon-γ-upregulated interleukin-15. / Musso, Tiziana; Calosso, Liliana; Zucca, Mario; Millesimo, Maura; Ravarino, Daniela; Giovarelli, Mirella; Malavasi, Fabio; Negro Ponzi, Alessandro; Paus, Ralf; Bulfone-Paus, Silvia.
In: Blood, Vol. 93, No. 10, 15.05.1999, p. 3531-3539.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human monocytes constitutively express membrane-bound, biologically active, and interferon-γ-upregulated interleukin-15
AU - Musso, Tiziana
AU - Calosso, Liliana
AU - Zucca, Mario
AU - Millesimo, Maura
AU - Ravarino, Daniela
AU - Giovarelli, Mirella
AU - Malavasi, Fabio
AU - Negro Ponzi, Alessandro
AU - Paus, Ralf
AU - Bulfone-Paus, Silvia
PY - 1999/5/15
Y1 - 1999/5/15
N2 - 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-α, 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.
AB - 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-α, 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.
UR - http://www.scopus.com/inward/record.url?scp=0033562382&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033562382&partnerID=8YFLogxK
M3 - Article
C2 - 10233906
AN - SCOPUS:0033562382
VL - 93
SP - 3531
EP - 3539
JO - Blood
JF - Blood
SN - 0006-4971
IS - 10
ER -