Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation

Hanno Hock, Melanie J. Hamblen, Heather M. Rooke, David Traver, Roderick T. Bronson, Scott Cameron, Stuart H. Orkin

Research output: Contribution to journalArticlepeer-review

313 Scopus citations

Abstract

We report essential roles of zinc finger transcription factor Gfi-1 in myeloid development. Gene-targeted Gfi-1-/- mice lack normal neutrophils and are highly susceptible to abscess formation by gram-positive bacteria. Arrested, morphologically atypical, Gr1+Mac1+ myeloid cells expand with age in the bone marrow. RNAs encoding primary but not secondary or tertiary neutrophil (granulocyte) granule proteins are expressed. The atypical Gr1+Mac1+ cell population shares characteristics of both the neutrophil and macrophage lineages and exhibits phagocytosis and respiratory burst activity. Reexpression of Gfi-1 in sorted Gfi-1-/- progenitors ex vivo rescues neutrophil differentiation in response to G-CSF. Thus, Gfi-1 not only promotes differentiation of neutrophils but also antagonizes traits of the alternate monocyte/macrophage program.

Original languageEnglish
Pages (from-to)109-120
Number of pages12
JournalImmunity
Volume18
Issue number1
DOIs
StatePublished - 1 Jan 2003
Externally publishedYes

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