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ERK Signaling Is Essential for Macrophage Development

Edward T Richardson1, Supriya Shukla2, Nancy Nagy2

  • 1Department of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, United States of America; Medical Scientist Training Program, Case Western Reserve University, Cleveland, Ohio, United States of America.

Plos One
|October 8, 2015
PubMed

Insights

Colony stimulating factor 1 (CSF-1) signaling is crucial for macrophage development. This study reveals that ERK1 and ERK2 signaling pathways are essential for CSF-1-driven proliferation and differentiation of bone marrow progenitors into macrophages.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophages are vital immune cells dependent on colony stimulating factor 1 (CSF-1) for development.
  • Intracellular signaling pathways governing CSF-1-induced macrophage differentiation and function are not fully understood.
  • The role of ERK1 and ERK2 in CSF-1 signaling and macrophage development requires elucidation.

Purpose of the Study:

  • To investigate the role of ERK1 and ERK2 signaling in CSF-1-dependent macrophage development.
  • To characterize a novel mouse model deficient in ERK1 and ERK2 in macrophages.
  • To determine the impact of ERK signaling on bone marrow progenitor proliferation and differentiation.

Main Methods:

  • Generation of Erk1(-/-) Erk2(flox/flox) Lyz2(Cre/Cre) mice for conditional deletion of ERK2 in macrophages.
  • Analysis of bone marrow progenitor populations and macrophage differentiation under CSF-1 stimulation.
  • Assessment of CSF-1-regulated gene expression in macrophages lacking ERK1/ERK2.

Main Results:

  • Mice with deleted ERK1/ERK2 in macrophages exhibited reduced numbers of developing macrophages.
  • A significant proportion of bone marrow progenitors showed impaired proliferation and differentiation in response to CSF-1.
  • CSF-1-induced expression of specific genes regulated by the ERK pathway was diminished in deficient macrophages.
  • Enrichment of myeloid cells, neutrophils, hematopoietic stem cells, and progenitor cells was observed in the bone marrow.

Conclusions:

  • The ERK1/ERK2 signaling pathway is critical for driving CSF-1-dependent proliferation of bone marrow progenitors for macrophage production.
  • Impaired ERK signaling reduces the ability of progenitors to proliferate and differentiate into macrophages.
  • These findings highlight the essential role of ERK1/ERK2 in regulating macrophage development.

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