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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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Evaluation of hematopoietic progenitor cells in the bone  marrow, spleen, and liver of transgenic mice and nontransgenic littermates. Standard CFU-GM (open bars) and BFU-E (closed bars) assays were  performed using spleen (A), liver (B), or bone marrow (C) cells from either IL-6–sIL-6R, IL-6, and sIL-6R mice or nontransgenic littermates, as  indicated in the figure. Triplicate cultures were scored after staining with  May-Grünwald-Giemsa (28) and are presented as mean values and standard deviation of one representative experiment out of three.
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Figure 5: Evaluation of hematopoietic progenitor cells in the bone marrow, spleen, and liver of transgenic mice and nontransgenic littermates. Standard CFU-GM (open bars) and BFU-E (closed bars) assays were performed using spleen (A), liver (B), or bone marrow (C) cells from either IL-6–sIL-6R, IL-6, and sIL-6R mice or nontransgenic littermates, as indicated in the figure. Triplicate cultures were scored after staining with May-Grünwald-Giemsa (28) and are presented as mean values and standard deviation of one representative experiment out of three.

Mentions: In view of the extramedullary hematopoiesis observed in liver and spleen, we investigated whether the continuous stimulation of the gp130 signal transducer affected committed hematopoietic progenitor cells of the granulocytic–monocytic and erythocytic lineages in different hematopoietic organs. The frequency of hematopoietic progenitor cells in the bone marrow, spleen, and liver of transgenic and nontransgenic mice was determined using in vitro clonogenic assays. The IL-6–sIL-6R-mediated gp130 stimulation had distinct effects on different hematopoietic lineages in extramedullary organs: the total number of CFU-GM and BFU-E in spleen and liver derived from IL-6–sIL-6R mice was increased ten times when compared with IL-6–sIL-6R single-transgenic mice and nontransgenic littermates (Fig. 5, A and B). Most interestingly, in the bone marrow, the relative and absolute number of clonogenic hematopoietic cells was not elevated in IL-6–sIL6R mice compared with IL-6 and sIL-6R single-transgenic and nontransgenic mice (Fig. 5 C).


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)

Evaluation of hematopoietic progenitor cells in the bone  marrow, spleen, and liver of transgenic mice and nontransgenic littermates. Standard CFU-GM (open bars) and BFU-E (closed bars) assays were  performed using spleen (A), liver (B), or bone marrow (C) cells from either IL-6–sIL-6R, IL-6, and sIL-6R mice or nontransgenic littermates, as  indicated in the figure. Triplicate cultures were scored after staining with  May-Grünwald-Giemsa (28) and are presented as mean values and standard deviation of one representative experiment out of three.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196150&req=5

Figure 5: Evaluation of hematopoietic progenitor cells in the bone marrow, spleen, and liver of transgenic mice and nontransgenic littermates. Standard CFU-GM (open bars) and BFU-E (closed bars) assays were performed using spleen (A), liver (B), or bone marrow (C) cells from either IL-6–sIL-6R, IL-6, and sIL-6R mice or nontransgenic littermates, as indicated in the figure. Triplicate cultures were scored after staining with May-Grünwald-Giemsa (28) and are presented as mean values and standard deviation of one representative experiment out of three.
Mentions: In view of the extramedullary hematopoiesis observed in liver and spleen, we investigated whether the continuous stimulation of the gp130 signal transducer affected committed hematopoietic progenitor cells of the granulocytic–monocytic and erythocytic lineages in different hematopoietic organs. The frequency of hematopoietic progenitor cells in the bone marrow, spleen, and liver of transgenic and nontransgenic mice was determined using in vitro clonogenic assays. The IL-6–sIL-6R-mediated gp130 stimulation had distinct effects on different hematopoietic lineages in extramedullary organs: the total number of CFU-GM and BFU-E in spleen and liver derived from IL-6–sIL-6R mice was increased ten times when compared with IL-6–sIL-6R single-transgenic mice and nontransgenic littermates (Fig. 5, A and B). Most interestingly, in the bone marrow, the relative and absolute number of clonogenic hematopoietic cells was not elevated in IL-6–sIL6R mice compared with IL-6 and sIL-6R single-transgenic and nontransgenic mice (Fig. 5 C).

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