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

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.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Ludin A,Itkin T,Gur-Cohen S,Mildner A,Shezen E,Golan K,Kollet O,Kalinkovich A,Porat Z,D'Uva G,Schajnovitz A,Voronov E,Brenner DA,Apte RN,Jung S,Lapidot T

doi

10.1038/ni.2408

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

1072-82

issue

11

eissn

1529-2908

issn

1529-2916

pii

ni.2408

journal_volume

13

pub_type

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