Abstract
Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)ε, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBPε locus. The predicted frame shift results in a truncation of the 32-kD major C/EBPε isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBPε deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBPε for the promyelocyte-myelocyte transition in myeloid differentiation.
Original language | English (US) |
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Pages (from-to) | 1847-1852 |
Number of pages | 6 |
Journal | Journal of Experimental Medicine |
Volume | 189 |
Issue number | 11 |
DOIs | |
State | Published - Jun 7 1999 |
Externally published | Yes |
Keywords
- Granulocyte
- Immunodeficiency
- Lactoferrin
- Myelopoiesis
- Neutrophil
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology