title: 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.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Aya
authors.initials: A
authors.lastname: Ludin
authors.forename: Tomer
authors.initials: T
authors.lastname: Itkin
authors.forename: Shiri
authors.initials: S
authors.lastname: Gur-Cohen
authors.forename: Alexander
authors.initials: A
authors.lastname: Mildner
authors.forename: Elias
authors.initials: E
authors.lastname: Shezen
authors.forename: Karin
authors.initials: K
authors.lastname: Golan
authors.forename: Orit
authors.initials: O
authors.lastname: Kollet
authors.forename: Alexander
authors.initials: A
authors.lastname: Kalinkovich
authors.forename: Ziv
authors.initials: Z
authors.lastname: Porat
authors.forename: Gabriele
authors.initials: G
authors.lastname: D'Uva
authors.forename: Amir
authors.initials: A
authors.lastname: Schajnovitz
authors.forename: Elena
authors.initials: E
authors.lastname: Voronov
authors.forename: David A
authors.initials: DA
authors.lastname: Brenner
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000276:immunology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000096:biosynthesis / Q000276:immunology; D005720:Gamma Rays; D005786:Gene Expression Regulation / Q000276:immunology / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000528:radiation effects; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology / Q000528:radiation effects
chemical_list: D000199:Actins; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D017382:Reactive Oxygen Species; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D015232:Dinoprostone