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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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Peripheral blood hematological data. White blood cell (A), neutrophil (B), platelet (C), red blood cell (D), and hemoglobin (E) values were  analyzed from six transgenic mice and nontransgenic littermates per group at ages indicated in the figure. Mean values with standard deviations are presented.
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Figure 6: Peripheral blood hematological data. White blood cell (A), neutrophil (B), platelet (C), red blood cell (D), and hemoglobin (E) values were analyzed from six transgenic mice and nontransgenic littermates per group at ages indicated in the figure. Mean values with standard deviations are presented.

Mentions: Peripheral blood cell numbers were determined at the age of 8, 16, and 24 wk in IL-6–sIL-6R mice and compared with numbers measured in IL-6 and sIL-6R single-transgenic mice and nontransgenic littermates. Whereas the peripheral blood cell numbers of single-transgenic and nontransgenic littermates were unchanged over the period of time tested, a most dramatic increase of white blood cells consisting mainly of neutrophilic granulocytes was observed in IL-6–sIL-6R mice (Fig. 6, A and B). At the age of 8 wk, there was no difference observed between IL-6–sIL-6R mice and single-transgenic mice and nontransgenic littermates. However, at the age of 16 wk, white blood cells and neutrophils increased by a factor of 10 and 17, respectively, and at the age of 24 wk by a factor of 27 and 48, respectively, in IL-6–sIL-6R mice. Platelets (Fig. 6 C), red blood cells (Fig. 6 D), and hemoglobin values (Fig. 6 E) of IL-6– sIL-6R mice increased by a factor of 2.1, 1.5, and 1.5, respectively, when compared with age-matched nontransgenic littermates and did not change in 16- and 24-wk-old mice. In single-transgenic animals, peripheral blood cell counts and hemoglobin values were not altered compared with nontransgenic mice (Fig. 6, C–E). Thus, the expanded pool of hematopoietic progenitor cells in IL-6–sIL-6R mice appears to retain its capacity to undergo proliferation and differentiation into mature blood cells, resulting in expansion of circulating blood cells.


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)

Peripheral blood hematological data. White blood cell (A), neutrophil (B), platelet (C), red blood cell (D), and hemoglobin (E) values were  analyzed from six transgenic mice and nontransgenic littermates per group at ages indicated in the figure. Mean values with standard deviations are presented.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2196150&req=5

Figure 6: Peripheral blood hematological data. White blood cell (A), neutrophil (B), platelet (C), red blood cell (D), and hemoglobin (E) values were analyzed from six transgenic mice and nontransgenic littermates per group at ages indicated in the figure. Mean values with standard deviations are presented.
Mentions: Peripheral blood cell numbers were determined at the age of 8, 16, and 24 wk in IL-6–sIL-6R mice and compared with numbers measured in IL-6 and sIL-6R single-transgenic mice and nontransgenic littermates. Whereas the peripheral blood cell numbers of single-transgenic and nontransgenic littermates were unchanged over the period of time tested, a most dramatic increase of white blood cells consisting mainly of neutrophilic granulocytes was observed in IL-6–sIL-6R mice (Fig. 6, A and B). At the age of 8 wk, there was no difference observed between IL-6–sIL-6R mice and single-transgenic mice and nontransgenic littermates. However, at the age of 16 wk, white blood cells and neutrophils increased by a factor of 10 and 17, respectively, and at the age of 24 wk by a factor of 27 and 48, respectively, in IL-6–sIL-6R mice. Platelets (Fig. 6 C), red blood cells (Fig. 6 D), and hemoglobin values (Fig. 6 E) of IL-6– sIL-6R mice increased by a factor of 2.1, 1.5, and 1.5, respectively, when compared with age-matched nontransgenic littermates and did not change in 16- and 24-wk-old mice. In single-transgenic animals, peripheral blood cell counts and hemoglobin values were not altered compared with nontransgenic mice (Fig. 6, C–E). Thus, the expanded pool of hematopoietic progenitor cells in IL-6–sIL-6R mice appears to retain its capacity to undergo proliferation and differentiation into mature blood cells, resulting in expansion of circulating blood cells.

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