Monocytes-macrophages that express ?-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow.Nat Immunol. 2012
Nat Immunol. 2012 Nov;13(11):1072-82. doi: 10.1038/ni.2408. Epub 2012 Sep 16.
Monocytes-macrophages that express ?-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow.
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.
SourceDepartment of Immunology, Weizmann Institute of Science, Rehovot, Israel.
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 ?-smooth muscle actin (?-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 ?-SMA(+) activated monocytes and macrophages that maintain HSPCs and protect them from exhaustion during alarm situations