Abstract
Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to IL-6. To identify cellular responses that are due to IL-6/sIL-6R but not to IL-6 alone, IL-6/sIL-6R double-transgenic mice were generated and compared with IL-6 single-transgenic mice. IL-6/sIL-6R transgenic mice develop a severe phenotype showing 1) marked hepatocellular hyperplasia frequently surrounded by peliosis and necrosis, 2) significant acceleration and aggravation of plasmacytoma formation, and 3) excessive activation of extramedullary hematopoiesis in spleen and liver followed by a subsequent increase of all cellular components in the peripheral blood. These in vivo data suggest that the sIL-6R recruits primarily unresponsive cell populations such as hematopoietic progenitor cells and hepatocytes to IL-6- induced proliferation, but also enhances the known mitogenic effect of IL-6 on plasma cells and thereby contributes to plasmacytoma formation.
| Original language | English |
|---|---|
| Pages (from-to) | 639-648 |
| Number of pages | 10 |
| Journal | American Journal of Pathology |
| Volume | 153 |
| Issue number | 2 |
| Publication status | Published - Aug 1998 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice. / Schirmacher, Peter; Peters, Malte; Ciliberto, Gennaro; Blessing, Manfred; Lotz, Johannes; Meyer Zum Büschenfelde, Karl Hermann; Rose-John, Stefan.
In: American Journal of Pathology, Vol. 153, No. 2, 08.1998, p. 639-648.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Hepatocellular hyperplasia, plasmacytoma formation, and extramedullary hematopoiesis in interleukin (IL)-6/soluble IL-6 receptor double-transgenic mice
AU - Schirmacher, Peter
AU - Peters, Malte
AU - Ciliberto, Gennaro
AU - Blessing, Manfred
AU - Lotz, Johannes
AU - Meyer Zum Büschenfelde, Karl Hermann
AU - Rose-John, Stefan
PY - 1998/8
Y1 - 1998/8
N2 - Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to IL-6. To identify cellular responses that are due to IL-6/sIL-6R but not to IL-6 alone, IL-6/sIL-6R double-transgenic mice were generated and compared with IL-6 single-transgenic mice. IL-6/sIL-6R transgenic mice develop a severe phenotype showing 1) marked hepatocellular hyperplasia frequently surrounded by peliosis and necrosis, 2) significant acceleration and aggravation of plasmacytoma formation, and 3) excessive activation of extramedullary hematopoiesis in spleen and liver followed by a subsequent increase of all cellular components in the peripheral blood. These in vivo data suggest that the sIL-6R recruits primarily unresponsive cell populations such as hematopoietic progenitor cells and hepatocytes to IL-6- induced proliferation, but also enhances the known mitogenic effect of IL-6 on plasma cells and thereby contributes to plasmacytoma formation.
AB - Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to IL-6. To identify cellular responses that are due to IL-6/sIL-6R but not to IL-6 alone, IL-6/sIL-6R double-transgenic mice were generated and compared with IL-6 single-transgenic mice. IL-6/sIL-6R transgenic mice develop a severe phenotype showing 1) marked hepatocellular hyperplasia frequently surrounded by peliosis and necrosis, 2) significant acceleration and aggravation of plasmacytoma formation, and 3) excessive activation of extramedullary hematopoiesis in spleen and liver followed by a subsequent increase of all cellular components in the peripheral blood. These in vivo data suggest that the sIL-6R recruits primarily unresponsive cell populations such as hematopoietic progenitor cells and hepatocytes to IL-6- induced proliferation, but also enhances the known mitogenic effect of IL-6 on plasma cells and thereby contributes to plasmacytoma formation.
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M3 - Article
C2 - 9708822
AN - SCOPUS:0031858640
VL - 153
SP - 639
EP - 648
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 2
ER -