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

doi:10.1038/ni.2408

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1072-1082
Number of pages	11
Journal	Nature Immunology
Volume	13
Issue number	11
DOIs	https://doi.org/10.1038/ni.2408
State	Published - Nov 2012
Externally published	Yes

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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, D. A., Apte, R. N., Jung, S., & Lapidot, T. (2012). Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow. Nature Immunology, 13(11), 1072-1082. https://doi.org/10.1038/ni.2408

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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.",

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

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doi = "10.1038/ni.2408",

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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 2012, 'Monocytes-macrophages that express α-smooth muscle actin preserve primitive hematopoietic cells in the bone marrow', Nature Immunology, vol. 13, no. 11, pp. 1072-1082. https://doi.org/10.1038/ni.2408

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AU - Ludin, Aya

AU - Itkin, Tomer

AU - Gur-Cohen, Shiri

AU - Mildner, Alexander

AU - Shezen, Elias

AU - Golan, Karin

AU - Kollet, Orit

AU - Kalinkovich, Alexander

AU - Porat, Ziv

AU - D'Uva, Gabriele

AU - Schajnovitz, Amir

AU - Voronov, Elena

AU - Brenner, David A.

AU - Apte, Ron N.

AU - Jung, Steffen

AU - Lapidot, Tsvee

PY - 2012/11

Y1 - 2012/11

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AB - 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.

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

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