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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
Nature Immunology13,1072–1082(2012)doi:10.1038/ni.2408
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 E2 (PGE2) 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 article in Nature Immunology:
http://www.nature.com/ni/journal/v13/n11/full/ni.2408.html
