Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor.
To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M.G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99:11872-11877) was composed of the interleukin 5 receptor alpha chain(+) (IL-5Ralpha(+)) and IL-5Ralpha(-) fractions, and the former was the hEoP. The IL-5Ralpha(+)CD34(+)CD38(+)IL-3Ralpha(+)CD45RA(-) hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5Ralpha(-) hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an "IL-5Ralpha-negative" criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders.
Mori
Yasuo
Y
Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Iwasaki
Hiromi
H
Kohno
Kentaro
K
Yoshimoto
Goichi
G
Kikushige
Yoshikane
Y
Okeda
Aki
A
Uike
Naokuni
N
Niiro
Hiroaki
H
Takenaka
Katsuto
K
Nagafuji
Koji
K
Miyamoto
Toshihiro
T
Harada
Mine
M
Takatsu
Kiyoshi
K
Akashi
Koichi
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism*; D001491:Basophils / Q000166:cytology / Q000378:metabolism; D019070:Cell Lineage; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D047209:Eosinophil Peroxidase / Q000378:metabolism; D004804:Eosinophils / Q000166:cytology* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D055014:Granulocyte-Macrophage Progenitor Cells / Q000166:cytology / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053666:Interleukin-5 Receptor alpha Subunit / Q000378:metabolism*; D008297:Male; D055015:Megakaryocyte-Erythroid Progenitor Cells / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
D015703:Antigens, CD; C485918:IL5RA protein, human; D053666:Interleukin-5 Receptor alpha Subunit; D014157:Transcription Factors; D047209:Eosinophil Peroxidase