Extramedullary expansion of hematopoietic progenitor cells in interleukin (IL)-6-sIL-6R double transgenic mice

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

Research output: Contribution to journalArticlepeer-review

157 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)755-766
Number of pages12
JournalJournal of Experimental Medicine
Volume185
Issue number4
DOIs
StatePublished - 17 Feb 1997
Externally publishedYes

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