Abstract
Erythropoiesis occurs in the presence of erythropoietin (EPO) without macrophages in vitro. In hematopoietic tissues, however, erythroid cells associate closely with stromal macrophages, forming erythroblastic islands via interactions with adhesion molecues. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated stromal macrophages of splenic red pulp of phlebotomized mice by injection with dichloromethylene disphosphohate encapsulated in multilamellar liposomes (CL2MDP-liposome). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. Colony assay revealed that the erthropoiesis was suppressed at the level of CFU-E. The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80+ macrophages began to appear in the red pulp. EPO mRNA was expressed in kidney but not in liver or spleen of phlebotomized mice injected with CL2MDP-liposome, and the serum EPO concentration in these mice was higher than that in phlebotomized mice. These findings suggest that abrogation of stromal macrophages by injection with CL2MDP-liposome impairs the splenic microenvironment for erythopoiesis induced by hypoxic stress, and this may be an excellent experimental model for further characterization of the in vivo role of splenic macrophages in erythropoiesis.
| Original language | English |
|---|---|
| Pages (from-to) | 464-470 |
| Number of pages | 7 |
| Journal | Journal of Leukocyte Biology |
| Volume | 68 |
| Issue number | 4 |
| Publication status | Published - 2000 |
| Externally published | Yes |
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Keywords
- Adhesion
- Erythroblasts
- Erythropoietin
- Hypoxia
- Microenvironment
ASJC Scopus subject areas
- Cell Biology
Cite this
Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome : An experimental model for studying the role of stromal macrophages in erythropoiesis. / Sadahira, Y.; Yasuda, T.; Yoshino, Tadashi; Manabe, T.; Takeishi, T.; Kobayashi, Y.; Ebe, Y.; Naito, M.
In: Journal of Leukocyte Biology, Vol. 68, No. 4, 2000, p. 464-470.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome
T2 - An experimental model for studying the role of stromal macrophages in erythropoiesis
AU - Sadahira, Y.
AU - Yasuda, T.
AU - Yoshino, Tadashi
AU - Manabe, T.
AU - Takeishi, T.
AU - Kobayashi, Y.
AU - Ebe, Y.
AU - Naito, M.
PY - 2000
Y1 - 2000
N2 - Erythropoiesis occurs in the presence of erythropoietin (EPO) without macrophages in vitro. In hematopoietic tissues, however, erythroid cells associate closely with stromal macrophages, forming erythroblastic islands via interactions with adhesion molecues. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated stromal macrophages of splenic red pulp of phlebotomized mice by injection with dichloromethylene disphosphohate encapsulated in multilamellar liposomes (CL2MDP-liposome). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. Colony assay revealed that the erthropoiesis was suppressed at the level of CFU-E. The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80+ macrophages began to appear in the red pulp. EPO mRNA was expressed in kidney but not in liver or spleen of phlebotomized mice injected with CL2MDP-liposome, and the serum EPO concentration in these mice was higher than that in phlebotomized mice. These findings suggest that abrogation of stromal macrophages by injection with CL2MDP-liposome impairs the splenic microenvironment for erythopoiesis induced by hypoxic stress, and this may be an excellent experimental model for further characterization of the in vivo role of splenic macrophages in erythropoiesis.
AB - Erythropoiesis occurs in the presence of erythropoietin (EPO) without macrophages in vitro. In hematopoietic tissues, however, erythroid cells associate closely with stromal macrophages, forming erythroblastic islands via interactions with adhesion molecues. To elucidate the role of macrophages in erythropoiesis, we selectively abrogated stromal macrophages of splenic red pulp of phlebotomized mice by injection with dichloromethylene disphosphohate encapsulated in multilamellar liposomes (CL2MDP-liposome). In the spleen, no erythropoietic activity occurred until 5 days after the treatment. Colony assay revealed that the erthropoiesis was suppressed at the level of CFU-E. The splenic erythropoietic activity gradually developed from day 6 after the treatment, when F4/80+ macrophages began to appear in the red pulp. EPO mRNA was expressed in kidney but not in liver or spleen of phlebotomized mice injected with CL2MDP-liposome, and the serum EPO concentration in these mice was higher than that in phlebotomized mice. These findings suggest that abrogation of stromal macrophages by injection with CL2MDP-liposome impairs the splenic microenvironment for erythopoiesis induced by hypoxic stress, and this may be an excellent experimental model for further characterization of the in vivo role of splenic macrophages in erythropoiesis.
KW - Adhesion
KW - Erythroblasts
KW - Erythropoietin
KW - Hypoxia
KW - Microenvironment
UR - http://www.scopus.com/inward/record.url?scp=0033771540&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033771540&partnerID=8YFLogxK
M3 - Article
C2 - 11037966
AN - SCOPUS:0033771540
VL - 68
SP - 464
EP - 470
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 4
ER -