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Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.

Publication ,  Journal Article
Cain, DW; Snowden, PB; Sempowski, GD; Kelsoe, G
Published in: PLoS One
2011

Normally, neutrophil pools are maintained by homeostatic mechanisms that require the transcription factor C/EBPα. Inflammation, however, induces neutrophilia through a distinct pathway of "emergency" granulopoiesis that is dependent on C/EBPβ. Here, we show in mice that alum triggers emergency granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R neutralization impairs proliferative responses of hematopoietic stem and progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM neutrophils, raising the possibility that HSPC responses to inflammation are an indirect result of the exhaustion of BM neutrophil stores. The induction of neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1, elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic responses indistinguishable from those induced by adjuvant. Notably, C/EBPβ, thought to be necessary for enhanced generative capacity of BM, is dispensable for increased proliferation of HSPC to alum or neutropenia, but plays a role in terminal neutrophil differentiation during granulopoietic recovery. We conclude that alum elicits a transient increase in G-CSF production via IL-1RI for the mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF for accelerated granulopoiesis.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

5

Start / End Page

e19957

Location

United States

Related Subject Headings

  • Neutropenia
  • Mice, Inbred C57BL
  • Mice
  • Leukopoiesis
  • Inflammation
  • Hematopoietic Stem Cells
  • Granulocytes
  • Granulocyte Colony-Stimulating Factor
  • General Science & Technology
  • Flow Cytometry
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cain, D. W., Snowden, P. B., Sempowski, G. D., & Kelsoe, G. (2011). Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS One, 6(5), e19957. https://doi.org/10.1371/journal.pone.0019957
Cain, Derek W., Pilar B. Snowden, Gregory D. Sempowski, and Garnett Kelsoe. “Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.PLoS One 6, no. 5 (2011): e19957. https://doi.org/10.1371/journal.pone.0019957.
Cain DW, Snowden PB, Sempowski GD, Kelsoe G. Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS One. 2011;6(5):e19957.
Cain, Derek W., et al. “Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism.PLoS One, vol. 6, no. 5, 2011, p. e19957. Pubmed, doi:10.1371/journal.pone.0019957.
Cain DW, Snowden PB, Sempowski GD, Kelsoe G. Inflammation triggers emergency granulopoiesis through a density-dependent feedback mechanism. PLoS One. 2011;6(5):e19957.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

5

Start / End Page

e19957

Location

United States

Related Subject Headings

  • Neutropenia
  • Mice, Inbred C57BL
  • Mice
  • Leukopoiesis
  • Inflammation
  • Hematopoietic Stem Cells
  • Granulocytes
  • Granulocyte Colony-Stimulating Factor
  • General Science & Technology
  • Flow Cytometry