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

Peters M, Schirmacher P, Goldschmitt J, Odenthal M, Peschel C, Fattori E, Ciliberto G, Dienes HP, Meyer zum Büschenfelde KH, Rose-John S - J. Exp. Med. (1997)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: I. Department of Medicine, University of Mainz, Germany.

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.

Show MeSH

Related in: MedlinePlus

Weight abnormalities in IL-6–sIL-6R mice. (A) An IL-6– sIL-6R double-transgenic mouse on the right side and a sIL-6R singletransgenic mouse on the left side at the age of 8 wk. (B) Total body  weight recorded of IL-6–sIL-6R mice, of single-transgenic mice, and of  nontransgenic littermates.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196150&req=5

Figure 1: Weight abnormalities in IL-6–sIL-6R mice. (A) An IL-6– sIL-6R double-transgenic mouse on the right side and a sIL-6R singletransgenic mouse on the left side at the age of 8 wk. (B) Total body weight recorded of IL-6–sIL-6R mice, of single-transgenic mice, and of nontransgenic littermates.

Mentions: The IL-6 transgene expression was regulated by the mouse metallothionein-1 promoter. The sIL-6R transgene expression was driven by the rat PEPCK promoter, which acts neonatally and permits evaluation of the influence of gene products after birth without intrauterine developmental effects. A distinct phenotype was observed in IL-6– sIL-6R mice compared with single-transgenic mice: IL-6 and sIL-6R single-transgenic and nontransgenic littermates (Fig. 1 A, left; data not shown) developed normally with respect to weight gain, food and water intake, appearance, and behavior. However, IL-6–sIL-6R mice (Fig. 1 A, right) were remarkably smaller compared with single-transgenic and nontransgenic littermates. When body weights were measured over a period of 20 wk, it became evident that the IL-6–sIL-6R mice developed reduced body weights as soon as 6 wk after birth (Fig. 1 B). At the age of 20 wk, mean values obtained in IL-6–sIL-6R mice were around 20–25 g compared with 40 g in single-transgenic and nontransgenic littermates (Fig. 1 B). Moreover, at autopsy and at histopathological analysis, IL-6–sIL-6R mice were found to have markedly reduced body fat in all regions of the organism compared with single-transgenic littermates (data not shown).


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

Peters M, Schirmacher P, Goldschmitt J, Odenthal M, Peschel C, Fattori E, Ciliberto G, Dienes HP, Meyer zum Büschenfelde KH, Rose-John S - J. Exp. Med. (1997)

Weight abnormalities in IL-6–sIL-6R mice. (A) An IL-6– sIL-6R double-transgenic mouse on the right side and a sIL-6R singletransgenic mouse on the left side at the age of 8 wk. (B) Total body  weight recorded of IL-6–sIL-6R mice, of single-transgenic mice, and of  nontransgenic littermates.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196150&req=5

Figure 1: Weight abnormalities in IL-6–sIL-6R mice. (A) An IL-6– sIL-6R double-transgenic mouse on the right side and a sIL-6R singletransgenic mouse on the left side at the age of 8 wk. (B) Total body weight recorded of IL-6–sIL-6R mice, of single-transgenic mice, and of nontransgenic littermates.
Mentions: The IL-6 transgene expression was regulated by the mouse metallothionein-1 promoter. The sIL-6R transgene expression was driven by the rat PEPCK promoter, which acts neonatally and permits evaluation of the influence of gene products after birth without intrauterine developmental effects. A distinct phenotype was observed in IL-6– sIL-6R mice compared with single-transgenic mice: IL-6 and sIL-6R single-transgenic and nontransgenic littermates (Fig. 1 A, left; data not shown) developed normally with respect to weight gain, food and water intake, appearance, and behavior. However, IL-6–sIL-6R mice (Fig. 1 A, right) were remarkably smaller compared with single-transgenic and nontransgenic littermates. When body weights were measured over a period of 20 wk, it became evident that the IL-6–sIL-6R mice developed reduced body weights as soon as 6 wk after birth (Fig. 1 B). At the age of 20 wk, mean values obtained in IL-6–sIL-6R mice were around 20–25 g compared with 40 g in single-transgenic and nontransgenic littermates (Fig. 1 B). Moreover, at autopsy and at histopathological analysis, IL-6–sIL-6R mice were found to have markedly reduced body fat in all regions of the organism compared with single-transgenic littermates (data not shown).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: I. Department of Medicine, University of Mainz, Germany.

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.

Show MeSH
Related in: MedlinePlus