Identification of eosinophil lineage-committed progenitors in the murine bone marrow.
Eosinophil lineage-committed progenitors (EoPs) are phenotypically isolatable in the steady-state murine bone marrow. Purified granulocyte/monocyte progenitors (GMPs) gave rise to eosinophils as well as neutrophils and monocytes at the single cell level. Within the short-term culture of GMPs, the eosinophil potential was found exclusively in cells activating the transgenic reporter for GATA-1, a transcription factor capable of instructing eosinophil lineage commitment. These GATA-1-activating cells possessed an IL-5Ralpha(+)CD34(+)c-Kit(lo) phenotype. Normal bone marrow cells also contained IL-5Ralpha(+)CD34(+)c-Kit(lo) EoPs that gave rise exclusively to eosinophils. EoPs significantly increased in number in response to helminth infection, suggesting that the EoP stage is physiologically involved in eosinophil production in vivo. EoPs expressed eosinophil-related genes, such as the eosinophil peroxidase and the major basic protein, but did not express basophil/mast cell-related mast cell proteases. The enforced retroviral expression of IL-5Ralpha in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Ralpha(+) GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Ralpha might be expressed specifically at the EoP stage as a result of commitment into the eosinophil lineage. The newly identified EoPs could be the cellular target in the treatment of a variety of disorders mediated by eosinophils.
Iwasaki
Hiromi
H
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Mizuno
Shin-ichi
S
Mayfield
Robin
R
Shigematsu
Hirokazu
H
Arinobu
Yojiro
Y
Seed
Brian
B
Gurish
Michael F
MF
Takatsu
Kiyoshi
K
Akashi
Koichi
K
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D019070:Cell Lineage / Q000502:physiology*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology*; D050981:Erythroid-Specific DNA-Binding Factors; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor; D042381:Granulocyte Precursor Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D053649:Receptors, Interleukin-5; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D014161:Transduction, Genetic
D018952:Antigens, CD34; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D014157:Transcription Factors; D019009:Proto-Oncogene Proteins c-kit