C/EBPβ is involved in the amplification of early granulocyte precursors during candidemia-induced "emergency" granulopoiesis

J Immunol. 2012 Nov 1;189(9):4546-55. doi: 10.4049/jimmunol.1103007. Epub 2012 Sep 28.

Abstract

Granulopoiesis is tightly regulated to meet host demands during both "steady-state" and "emergency" situations, such as infections. The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPβ is required are unknown. In this study, a novel flow cytometric method was developed that successfully dissected mouse bone marrow cells undergoing granulopoiesis into five distinct subpopulations (#1-5) according to their levels of c-Kit and Ly-6G expression. After the induction of candidemia, rapid mobilization of mature granulocytes and an increase in early granulocyte precursors accompanied by cell cycle acceleration was followed by a gradual increase in granulocytes originating from the immature populations. Upon infection, C/EBPβ was upregulated at the protein level in all the granulopoietic subpopulations. The rapid increase in immature subpopulations #1 and #2 observed in C/EBPβ knockout mice at 1 d postinfection was attenuated. Candidemia-induced cell cycle acceleration and proliferation of hematopoietic stem/progenitors were also impaired. Taken together, these data suggest that C/EBPβ is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / deficiency
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / physiology*
  • Candidemia / immunology*
  • Candidemia / metabolism
  • Candidemia / pathology*
  • Flow Cytometry / methods
  • Gene Amplification / immunology*
  • Granulocytes / immunology*
  • Granulocytes / metabolism
  • Granulocytes / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid Progenitor Cells / immunology*
  • Myeloid Progenitor Cells / metabolism
  • Myeloid Progenitor Cells / pathology*
  • Time Factors

Substances

  • CCAAT-Enhancer-Binding Protein-beta