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Eosinophils from lineage-ablated Delta dblGATA bone marrow progenitors: the dblGATA enhancer in the promoter of GATA-1 is not essential for differentiation ex vivo.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2007 Aug 01; Vol. 179 (3), pp. 1693-9. - Publication Year :
- 2007
-
Abstract
- A critical role for eosinophils in remodeling of allergic airways was observed in vivo upon disruption of the dblGATA enhancer that regulates expression of GATA-1, which resulted in an eosinophil-deficient phenotype in the DeltadblGATA mouse. We demonstrate here that bone marrow progenitors isolated from DeltadblGATA mice can differentiate into mature eosinophils when subjected to cytokine stimulation ex vivo. Cultured DeltadblGATA eosinophils contain cytoplasmic granules with immunoreactive major basic protein and they express surface Siglec F and transcripts encoding major basic protein, eosinophil peroxidase, and GATA-1, -2, and -3 to an extent indistinguishable from cultured wild-type eosinophils. Fibroblast coculture and bone marrow cross-transplant experiments indicate that the in vivo eosinophil deficit is an intrinsic progenitor defect, and remains unaffected by interactions with stromal cells. Interestingly, and in contrast to those from the wild type, a majority of the GATA-1 transcripts from cultured DeltadblGATA progenitors express a variant GATA-1 transcript that includes a first exon (1E(B)), located approximately 3700 bp downstream to the previously described first exon found in hemopoietic cells (1E(A)) and approximately 42 bp upstream to another variant first exon, 1E(C). These data suggest that cultured progenitors are able to circumvent the effects of the DeltadblGATA ablation by using a second, more proximal, promoter and use this mechanism to generate quantities of GATA-1 that will support eosinophil growth and differentiation.
- Subjects :
- Animals
Binding Sites genetics
Binding Sites immunology
Bone Marrow Cells cytology
Bone Marrow Cells metabolism
Cell Differentiation immunology
Cell Lineage immunology
Cell Proliferation
Cells, Cultured
Coculture Techniques
Eosinophils cytology
Eosinophils immunology
Eosinophils transplantation
GATA1 Transcription Factor physiology
GATA2 Transcription Factor genetics
GATA3 Transcription Factor genetics
Hematopoietic Stem Cells cytology
Hematopoietic Stem Cells metabolism
Interleukin-5 physiology
Male
Mice
Mice, Inbred BALB C
Mice, Mutant Strains
Th2 Cells immunology
Bone Marrow Cells immunology
Cell Differentiation genetics
Cell Lineage genetics
Enhancer Elements, Genetic
Eosinophils metabolism
GATA1 Transcription Factor genetics
Hematopoietic Stem Cells immunology
Promoter Regions, Genetic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 179
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 17641035
- Full Text :
- https://doi.org/10.4049/jimmunol.179.3.1693