Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow

Nat Immunol. 2012 Nov;13(11):1072-82. doi: 10.1038/ni.2408. Epub 2012 Sep 16.

Abstract

Hematopoietic stem and progenitor cells (HSPCs) are regulated by various bone marrow stromal cell types. Here we identified rare activated bone marrow monocytes and macrophages with high expression of α-smooth muscle actin (α-SMA) and the cyclooxygenase COX-2 that were adjacent to primitive HSPCs. These myeloid cells resisted radiation-induced cell death and further upregulated COX-2 expression under stress conditions. COX-2-derived prostaglandin E(2) (PGE(2)) prevented HSPC exhaustion by limiting the production of reactive oxygen species (ROS) via inhibition of the kinase Akt and higher stromal-cell expression of the chemokine CXCL12, which is essential for stem-cell quiescence. Our study identifies a previously unknown subset of α-SMA(+) activated monocytes and macrophages that maintain HSPCs and protect them from exhaustion during alarm situations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics
  • Actins / immunology*
  • Animals
  • Bone Marrow / immunology*
  • Bone Marrow / metabolism
  • Bone Marrow / radiation effects
  • Cell Communication / genetics
  • Cell Communication / immunology
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Cell Survival / genetics
  • Cell Survival / immunology
  • Cell Survival / radiation effects
  • Chemokine CXCL12 / genetics
  • Chemokine CXCL12 / immunology
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / immunology
  • Dinoprostone / biosynthesis
  • Dinoprostone / immunology
  • Gamma Rays
  • Gene Expression Regulation / immunology
  • Gene Expression Regulation / radiation effects
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • Hematopoietic Stem Cells / radiation effects
  • Macrophages / cytology
  • Macrophages / immunology*
  • Macrophages / radiation effects
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / immunology
  • Mesenchymal Stem Cells / radiation effects
  • Mice
  • Monocytes / cytology
  • Monocytes / immunology*
  • Monocytes / radiation effects
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / immunology
  • Reactive Oxygen Species / immunology
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Signal Transduction / radiation effects

Substances

  • Actins
  • Chemokine CXCL12
  • Cxcl12 protein, mouse
  • Reactive Oxygen Species
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Proto-Oncogene Proteins c-akt
  • Dinoprostone