The Journal of Experimental Medicine
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Published online 13 June 2005 doi:10.1084/jem.20050548
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 12, 1891-1897
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BRIEF DEFINITIVE REPORT

 Identification of eosinophil lineage–committed progenitors in the murine bone marrow

Hiromi Iwasaki1,2, Shin-ichi Mizuno1, Robin Mayfield3, Hirokazu Shigematsu1, Yojiro Arinobu1, Brian Seed3, Michael F. Gurish4, Kiyoshi Takatsu5, and Koichi Akashi1,2

1 Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115
2 Center for Cellular and Molecular Medicine, Kyushu University Hospital, Fukuoka 812-8582, Japan
3 Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02115
4 Division of Rheumatology, Allergy and Immunology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
5 Division of Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

CORRESPONDENCE Koichi Akashi: koichi_akashi{at}dfci.harvard.edu

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-5R{alpha}+CD34+c-Kitlo phenotype. Normal bone marrow cells also contained IL-5R{alpha}+CD34+c-Kitlo 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-5R{alpha} in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5R{alpha}+ GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5R{alpha} 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.

Abbreviations used: CLP, common lymphoid progenitor; CMP, common myeloid progenitor; EoP, eosinophil lineage–committed progenitor; EoPO, eosinophil peroxidase; GMP, granulocyte/monocyte progenitor; HSC, hematopoietic stem cell; MBP, major basic proteins; MEP, megakaryocyte/erythrocyte progenitor.


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