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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.

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Organ weight and gross morphology of liver and spleen. Liver (A) and spleen (B) weight of IL-6–sIL-6R, IL-6, and sIL-6R mice and nontransgenic littermates. Organ weight is presented as liver weight/total body weight and spleen weight/total body weight, respectively. Gross morphology  of livers and spleens of sIL-6R mice (C, left) and IL-6–sIL-6R mice (C, right) at 12 wk of age.
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Figure 2: Organ weight and gross morphology of liver and spleen. Liver (A) and spleen (B) weight of IL-6–sIL-6R, IL-6, and sIL-6R mice and nontransgenic littermates. Organ weight is presented as liver weight/total body weight and spleen weight/total body weight, respectively. Gross morphology of livers and spleens of sIL-6R mice (C, left) and IL-6–sIL-6R mice (C, right) at 12 wk of age.

Mentions: Most remarkably, at the age of 4–6 wk, IL-6–sIL6R mice displayed distended abdominal regions (Fig. 1 A). Single-transgenic and nontransgenic littermates were normal in this respect. The abdominal distension was caused by a marked increase of liver and spleen weights relative to the total body weight. Time course experiments (Fig. 2, A and B) revealed steadily increasing relative liver and spleen weights in IL-6–sIL-6R mice, while the respective relative organ weights in single-transgenic and nontransgenic littermates were unchanged. At wk 20, the relative liver weight (Fig. 2 A) had duplicated and the relative spleen weight (Fig. 2 B) had increased by a factor of 5 when compared with single-transgenic and nontransgenic littermates.


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)

Organ weight and gross morphology of liver and spleen. Liver (A) and spleen (B) weight of IL-6–sIL-6R, IL-6, and sIL-6R mice and nontransgenic littermates. Organ weight is presented as liver weight/total body weight and spleen weight/total body weight, respectively. Gross morphology  of livers and spleens of sIL-6R mice (C, left) and IL-6–sIL-6R mice (C, right) at 12 wk of age.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 2: Organ weight and gross morphology of liver and spleen. Liver (A) and spleen (B) weight of IL-6–sIL-6R, IL-6, and sIL-6R mice and nontransgenic littermates. Organ weight is presented as liver weight/total body weight and spleen weight/total body weight, respectively. Gross morphology of livers and spleens of sIL-6R mice (C, left) and IL-6–sIL-6R mice (C, right) at 12 wk of age.
Mentions: Most remarkably, at the age of 4–6 wk, IL-6–sIL6R mice displayed distended abdominal regions (Fig. 1 A). Single-transgenic and nontransgenic littermates were normal in this respect. The abdominal distension was caused by a marked increase of liver and spleen weights relative to the total body weight. Time course experiments (Fig. 2, A and B) revealed steadily increasing relative liver and spleen weights in IL-6–sIL-6R mice, while the respective relative organ weights in single-transgenic and nontransgenic littermates were unchanged. At wk 20, the relative liver weight (Fig. 2 A) had duplicated and the relative spleen weight (Fig. 2 B) had increased by a factor of 5 when compared with single-transgenic and nontransgenic littermates.

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