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.
Extramedullary Expansion of Hematopoietic Progenitor Cells in Interleukin (IL)-6–sIL-6R Double Transgenic Mice
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.
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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