Soluble cytokine receptors modulate the activity of their cognate ligands. Interleukin (IL)-6 in association with the soluble IL-6 receptor (sIL-6R) can activate cells expressing the gp130 signal transducer lacking the specific IL-6R. To investigate the function of the IL-6–sIL-6R complex in vivo and to discriminate the function of the IL-6–sIL-6R complex from the function of IL-6 alone, we have established a transgenic mouse model. Double-transgenic mice coexpressing IL-6 and sIL-6R were generated and compared with IL-6 and sIL-6R single-transgenic mice. The main phenotype found in IL-6–sIL-6R mice was a dramatic increase of extramedullary hematopoietic progenitor cells in liver and spleen but not in the bone marrow. In IL-6 single-transgenic mice and sIL-6R single-transgenic mice no such effects were observed. The high numbers of hematopoietic progenitor cells were reflected by a strong increase of peripheral blood cell numbers. Therefore, activators of the gp130 signal transducer like the IL-6–IL-6R complex may represent most powerful stimulators for extramedullary hematopoietic progenitor cells. gp130 activators may become important for the expansion of hematopoietic progenitor cells in vivo and in vitro.
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17 February 1997
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February 17 1997
Extramedullary Expansion of Hematopoietic Progenitor Cells in Interleukin (IL)-6–sIL-6R Double Transgenic Mice
Malte Peters,
Malte Peters
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Peter Schirmacher,
Peter Schirmacher
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Jutta Goldschmitt,
Jutta Goldschmitt
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Margarete Odenthal,
Margarete Odenthal
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Christian Peschel,
Christian Peschel
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Elena Fattori,
Elena Fattori
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Gennaro Ciliberto,
Gennaro Ciliberto
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Hans-Peter Dienes,
Hans-Peter Dienes
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Karl-Hermann Meyer zum Büschenfelde,
Karl-Hermann Meyer zum Büschenfelde
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Stefan Rose-John
Stefan Rose-John
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
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Malte Peters
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Peter Schirmacher
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Jutta Goldschmitt
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Margarete Odenthal
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Christian Peschel
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Elena Fattori
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Gennaro Ciliberto
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Hans-Peter Dienes
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Karl-Hermann Meyer zum Büschenfelde
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Stefan Rose-John
From the *I. Department of Medicine, Section of Pathophysiology; ‡Institute of Pathology; §III. Department of Medicine, University of Mainz, D-55101 Mainz, Germany; ‖Instituto di Ricerche di Biologia Moleculare P. Angeletti, Pomezia, Rome, Italy; and ¶Institute of Pathology, University of Cologne, 51123 Cologne, Germany
Address correspondence to Malte Peters, I. Department of Medicine, Section of Pathophysiology, University of Mainz, Obere Zahlbacher Strasse 63, D-55101 Mainz, Germany.
1 Abbreviations used in this paper: CNTF, ciliary neurotrophic factor; CT-1, cardiotrophin-1; LIF, leukemia inhibitory factor; OSM, oncostatin M; PEPCK, phosphoenolpyruvate carboxykinase; sIL-6R, soluble interleukin-6 receptor; TNF-R, tumor necrosis factor receptor.
Received:
October 30 1996
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (4): 755–766.
Article history
Received:
October 30 1996
Citation
Malte Peters, Peter Schirmacher, Jutta Goldschmitt, Margarete Odenthal, Christian Peschel, Elena Fattori, Gennaro Ciliberto, Hans-Peter Dienes, Karl-Hermann Meyer zum Büschenfelde, Stefan Rose-John; Extramedullary Expansion of Hematopoietic Progenitor Cells in Interleukin (IL)-6–sIL-6R Double Transgenic Mice. J Exp Med 17 February 1997; 185 (4): 755–766. doi: https://doi.org/10.1084/jem.185.4.755
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