Extramedullary expansion of hematopoietic progenitor cells in interleukin (IL)-6-sIL-6R double transgenic mice.
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.
Peters
M
M
I. Department of Medicine, University of Mainz, Germany.
Schirmacher
P
P
Goldschmitt
J
J
Odenthal
M
M
Peschel
C
C
Fattori
E
E
Ciliberto
G
G
Dienes
H P
HP
Meyer zum Büschenfelde
K H
KH
Rose-John
S
S
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001835:Body Weight; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation; D050822:Cytokine Receptor gp130; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D015398:Signal Transduction; D013154:Spleen / Q000473:pathology
D015703:Antigens, CD; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D050822:Cytokine Receptor gp130