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Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor.

Mori Y, Iwasaki H, Kohno K, Yoshimoto G, Kikushige Y, Okeda A, Uike N, Niiro H, Takenaka K, Nagafuji K, Miyamoto T, Harada M, Takatsu K, Akashi K - J. Exp. Med. (2008)

Bottom Line: Weissman. 2002.Proc.Natl.

View Article: PubMed Central - PubMed

Affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.

ABSTRACT
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.

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The in vivo expansion of hEoP in the bone marrow of eosinophilia patients. (A) The percentage of the hEoP population in the bone marrow CD34+ fraction. Eosinophila patients possessed approximately fourfold increased numbers of hEoPs (horizontal lines indicate means). Patients' characteristics are summarized in Table I. (B) The lineal relationship between the hEoP and other myeloid progenitor populations. The original hCMP (shaded) contained the hEoP. The revised hCMP is defined as the IL-5Rα− fraction of the original hCMP. The hEoP develops from the hCMP or its upstream MPP independent of the hGMP and the hMEP.
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fig6: The in vivo expansion of hEoP in the bone marrow of eosinophilia patients. (A) The percentage of the hEoP population in the bone marrow CD34+ fraction. Eosinophila patients possessed approximately fourfold increased numbers of hEoPs (horizontal lines indicate means). Patients' characteristics are summarized in Table I. (B) The lineal relationship between the hEoP and other myeloid progenitor populations. The original hCMP (shaded) contained the hEoP. The revised hCMP is defined as the IL-5Rα− fraction of the original hCMP. The hEoP develops from the hCMP or its upstream MPP independent of the hGMP and the hMEP.

Mentions: To evaluate whether the hEoP contributes toward eosinophil production in vivo, we enumerated the number of hEoPs in the bone marrow of eosinophilia patients. Patients' characteristics are summarized in Table I. In normal bone marrow samples, the hEoP population accounted for only 0.033% of bone marrow MNCs or 2.38% of Lin−CD34+ cells, respectively (Table I and Fig. 6 A). We analyzed 15 patients with eosinophilia: 5 patients with hypereosinophilic syndrome (HES), 2 patients with T cell malignancies, 1 chronic myelogenous leukemia patient in accelerated phase, 2 patients with Churg-Strauss syndrome, and 5 eosinophilia patients with unknown etiology. The FIP1L1/PDGFRα fusion gene was not detected in any of these patients. The blood eosinophil count was 13,799 μl, and eosinophil lineage cells accounted for 38.4% of whole bone marrow cells on average (Table I). The bone marrow hEoP in eosinophilia patients consisted of 0.125% of MNCs or 7.44% of Lin−CD34+ cells, respectively (Table I and Fig. 6 A). Thus, eosinophilia patients possessed three- to fourfold higher numbers of hEoPs compared with normal controls (P < 0.01; Fig. 6 A). These data suggest that the hEoP stage is actively involved in generation of eosinophils in patients with eosinophilia.


Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor.

Mori Y, Iwasaki H, Kohno K, Yoshimoto G, Kikushige Y, Okeda A, Uike N, Niiro H, Takenaka K, Nagafuji K, Miyamoto T, Harada M, Takatsu K, Akashi K - J. Exp. Med. (2008)

The in vivo expansion of hEoP in the bone marrow of eosinophilia patients. (A) The percentage of the hEoP population in the bone marrow CD34+ fraction. Eosinophila patients possessed approximately fourfold increased numbers of hEoPs (horizontal lines indicate means). Patients' characteristics are summarized in Table I. (B) The lineal relationship between the hEoP and other myeloid progenitor populations. The original hCMP (shaded) contained the hEoP. The revised hCMP is defined as the IL-5Rα− fraction of the original hCMP. The hEoP develops from the hCMP or its upstream MPP independent of the hGMP and the hMEP.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2626675&req=5

fig6: The in vivo expansion of hEoP in the bone marrow of eosinophilia patients. (A) The percentage of the hEoP population in the bone marrow CD34+ fraction. Eosinophila patients possessed approximately fourfold increased numbers of hEoPs (horizontal lines indicate means). Patients' characteristics are summarized in Table I. (B) The lineal relationship between the hEoP and other myeloid progenitor populations. The original hCMP (shaded) contained the hEoP. The revised hCMP is defined as the IL-5Rα− fraction of the original hCMP. The hEoP develops from the hCMP or its upstream MPP independent of the hGMP and the hMEP.
Mentions: To evaluate whether the hEoP contributes toward eosinophil production in vivo, we enumerated the number of hEoPs in the bone marrow of eosinophilia patients. Patients' characteristics are summarized in Table I. In normal bone marrow samples, the hEoP population accounted for only 0.033% of bone marrow MNCs or 2.38% of Lin−CD34+ cells, respectively (Table I and Fig. 6 A). We analyzed 15 patients with eosinophilia: 5 patients with hypereosinophilic syndrome (HES), 2 patients with T cell malignancies, 1 chronic myelogenous leukemia patient in accelerated phase, 2 patients with Churg-Strauss syndrome, and 5 eosinophilia patients with unknown etiology. The FIP1L1/PDGFRα fusion gene was not detected in any of these patients. The blood eosinophil count was 13,799 μl, and eosinophil lineage cells accounted for 38.4% of whole bone marrow cells on average (Table I). The bone marrow hEoP in eosinophilia patients consisted of 0.125% of MNCs or 7.44% of Lin−CD34+ cells, respectively (Table I and Fig. 6 A). Thus, eosinophilia patients possessed three- to fourfold higher numbers of hEoPs compared with normal controls (P < 0.01; Fig. 6 A). These data suggest that the hEoP stage is actively involved in generation of eosinophils in patients with eosinophilia.

Bottom Line: Weissman. 2002.Proc.Natl.

View Article: PubMed Central - PubMed

Affiliation: Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus