Erythropoietin induces the expansion of c-kit+ progenitors for myeloid and erythroid cells, but not for lymphoid cells, in the bone marrow and liver.
In humans, the numbers of erythrocytes and granulocytes, but not that of lymphocytes, tend to increase in parallel. To determine the mechanism, we investigated how the administration of erythropoietin induces the expansion of erythroid cells and other lineage cells in the bone marrow, liver, and other organs of mice. When mice were injected twice (days 1 and 2) with erythropoietin at a dose of 20 or 200 IU/day/ mouse, a prominent expansion of TER 19+ (erythroid cells) and Gr-1high cells (granulocytes) occurred in the liver, spleen, and bone marrow day 3 after the initial injection. On the other hand, lymphoid cells, including NK cells, extrathymic T cells, and conventional T cells, did not expand. In parallel with the expansion of erythroid cells and granulocytes, the levels of c-kit(+)Lin- cells increased in the liver and bone marrow. Despite the increase in the proportion of c-kit(+) Lin(-) cells, the generation of lymphocytes (e.g., T cells) decreased when such bone marrow cells were injected to scid mice. These results suggest that erythropoietin has the ability to induce the expansion of not only erythroid cells but also granulocytes in the liver, spleen, and bone marrow. Furthermore, c-kit+ progenitors which may commit themselves to erythroid and myeloid cells, but not to lymphoid cells, were also activated in the liver and bone marrow of mice treated with erythropoietin.
Koya
T
T
Department of Immunology, Niigata University School of Medicine, Japan.
Narita
J
J
Honda
S
S
Watanabe
H
H
Arakawa
M
M
Abo
T
T
D000328:Adult; D000818:Animals; D001853:Bone Marrow; D019070:Cell Lineage / Q000187:drug effects*; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D019891:Leukopoiesis / Q000187:drug effects; D008099:Liver / Q000166:cytology*; D008214:Lymphocytes / Q000166:cytology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit
D004921:Erythropoietin; D019009:Proto-Oncogene Proteins c-kit