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

Aya Ludin, Tomer Itkin, Shiri Gur-Cohen, Alexander Mildner, Elias Shezen, Karin Golan, Orit Kollet, Alexander Kalinkovich, Ziv Porat, Gabriele D'Uva, Amir Schajnovitz, Elena Voronov, David A. Brenner, Ron N. Apte, Steffen Jung, Tsvee Lapidot

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

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.

Original languageEnglish
Pages (from-to)1072-1082
Number of pages11
JournalNature Immunology
Volume13
Issue number11
DOIs
StatePublished - 1 Nov 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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