Identification of eosinophil lineage–committed progenitors in the murine bone marrow
Open Access
- 13 June 2005
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 201 (12), 1891-1897
- https://doi.org/10.1084/jem.20050548
Abstract
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-5Rα+CD34+c-Kitlo phenotype. Normal bone marrow cells also contained IL-5Rα+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-5Rα in GMPs did not enhance the frequency of eosinophil lineage read-outs, whereas IL-5Rα+ GMPs displayed normal neutrophil/monocyte differentiation in the presence of IL-5 alone. Thus, IL-5Rα 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.Keywords
This publication has 36 references indexed in Scilit:
- Anti–interleukin-5 (mepolizumab) therapy for hypereosinophilic syndromes☆Journal of Allergy and Clinical Immunology, 2004
- GATA-1 Converts Lymphoid and Myelomonocytic Progenitors into the Megakaryocyte/Erythrocyte LineagesImmunity, 2003
- Making Eosinophils Through Subtle Shifts in Transcription Factor ExpressionThe Journal of Experimental Medicine, 2002
- Antagonism between C/EBPβ and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitorsGenes & Development, 2000
- Therapeutic efficacy of an anti–IL-5 monoclonal antibody delivered into the respiratory tract in a murine model of asthma☆☆☆★Journal of Allergy and Clinical Immunology, 1999
- Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.The Journal of Experimental Medicine, 1996
- Differentiation in vitro of hybrid eosinophil/basophil granulocytes: autocrine function of an eosinophil developmental intermediate.The Journal of Experimental Medicine, 1995
- Eosinophilia in transgenic mice expressing interleukin 5.The Journal of Experimental Medicine, 1990
- Characterization of the murine interleukin 5 receptor by using a monoclonal antibodyInternational Immunology, 1990
- MECHANISM OF EOSINOPHILIAThe Journal of Experimental Medicine, 1970