CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages

被引：189
作者：
Lei, Fengyang [1 ]
Cui, Naiwen [2 ]
Zhou, Chengxin [1 ]
Chodosh, James [1 ]
Vavvas, Demetrios G. [1 ]
Paschalis, Eleftherios I. [1 ]
机构：
[1] Harvard Med Sch, Massachusetts Eye & Ear, Dept Ophthalmol, Boston, MA 02114 USA
[2] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2020年 / 117卷 / 38期
关键词：
microglia; macrophages; CSF1R; hematopoiesis; CNS; REGENERATION; IMPROVES; CELL;
D O I：
10.1073/pnas.1922788117
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Colony-stimulating factor 1 receptor (CSF1R) inhibition has been proposed as a method for microglia depletion, with the assumption that it does not affect peripheral immune cells. Here, we show that CSF1R inhibition by PLX5622 indeed affects the myeloid and lymphoid compartments, causes long-term changes in bone marrow-derived macrophages by suppressing interleukin 1 beta, CD68, and phagocytosis but not CD208, following exposure to endotoxin, and also reduces the population of resident and interstitial macrophages of peritoneum, lung, and liver but not spleen. Thus, small-molecule CSF1R inhibition is not restricted to microglia, causing strong effects on circulating and tissue macrophages that perdure long after cessation of the treatment. Given that peripheral monocytes repopulate the central nervous system after CSF1R inhibition, these changes have practical implications for relevant experimental data.
引用
收藏
页码：23336 / 23338
页数：3
相关论文
共 19 条
  • [1] Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities
    Bain, Calum C.
    Hawley, Catherine A.
    Garner, Hannah
    Scott, Charlotte L.
    Schridde, Anika
    Steers, Nicholas J.
    Mack, Matthias
    Joshi, Anagha
    Guilliams, Martin
    Mowat, Allan Mc I.
    Geissmann, Frederic
    Jenkins, Stephen J.
    [J]. NATURE COMMUNICATIONS, 2016, 7
  • [2] Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury
    Bellver-Landete, Victor
    Bretheau, Floriane
    Mailhot, Benoit
    Vallieres, Nicolas
    Lessard, Martine
    Janelle, Marie-Eve
    Vernoux, Nathalie
    Tremblay, Marie-Eve
    Fuehrmann, Tobias
    Shoichet, Molly S.
    Lacroix, Steve
    [J]. NATURE COMMUNICATIONS, 2019, 10 (1)
  • [3] Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches
    Chakarov, Svetoslav
    Lim, Hwee Ying
    Tan, Leonard
    Lim, Sheau Yng
    See, Peter
    Lum, Josephine
    Zhang, Xiao-Meng
    Foo, Shihui
    Nakamizo, Satoshi
    Duan, Kaibo
    Kong, Wan Ting
    Gentek, Rebecca
    Balachander, Akhila
    Carbajo, Daniel
    Bleriot, Camille
    Malleret, Benoit
    Tam, John Kit Chung
    Baig, Sonia
    Shabeer, Muhammad
    Toh, Sue-Anne Ee Shiow
    Schlitzer, Andreas
    Larbi, Anis
    Marichal, Thomas
    Malissen, Bernard
    Chen, Jinmiao
    Poidinger, Michael
    Kabashima, Kenji
    Bajenoff, Marc
    Ng, Lai Guan
    Angeli, Veronique
    Ginhoux, Florent
    [J]. SCIENCE, 2019, 363 (6432) : 1190 - +
  • [4] Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice
    Dagher, Nabil N.
    Najafi, Allison R.
    Kayala, Kara M. Neely
    Elmore, Monica R. P.
    White, Terra E.
    Medeiros, Rodrigo
    West, Brian L.
    Green, Kim N.
    [J]. JOURNAL OF NEUROINFLAMMATION, 2015, 12
  • [5] Colony-Stimulating Factor 1 Receptor Signaling Is Necessary for Microglia Viability, Unmasking a Microglia Progenitor Cell in the Adult Brain
    Elmore, Monica R. P.
    Najafi, Allison R.
    Koike, Maya A.
    Dagher, Nabil N.
    Spangenberg, Elizabeth E.
    Rice, Rachel A.
    Kitazawa, Masashi
    Matusow, Bernice
    Nguyen, Hoa
    West, Brian L.
    Green, Kim N.
    [J]. NEURON, 2014, 82 (02) : 380 - 397
  • [6] High-resolution intravital imaging reveals that blood-derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury
    Evans, Teresa A.
    Barkauskas, Deborah S.
    Myers, Jay T.
    Hare, Elisabeth G.
    You, Jing Qiang
    Ransohoff, Richard M.
    Huang, Alex Y.
    Silver, Jerry
    [J]. EXPERIMENTAL NEUROLOGY, 2014, 254 : 109 - 120
  • [7] Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages
    Gautier, Emmanuel L.
    Shay, Tal
    Miller, Jennifer
    Greter, Melanie
    Jakubzick, Claudia
    Ivanov, Stoyan
    Helft, Julie
    Chow, Andrew
    Elpek, Kutlu G.
    Gordonov, Simon
    Mazloom, Amin R.
    Ma'ayan, Avi
    Chua, Wei-Jen
    Hansen, Ted H.
    Turley, Shannon J.
    Merad, Miriam
    Randolph, Gwendalyn J.
    [J]. NATURE IMMUNOLOGY, 2012, 13 (11) : 1118 - 1128
  • [8] Three Unique Interstitial Macrophages in the Murine Lung at Steady State
    Gibbings, Sophie L.
    Thomas, Stacey M.
    Atif, Shaikh M.
    McCubbrey, Alexandra L.
    Desch, A. Nicole
    Danhorn, Thomas
    Leach, Sonia M.
    Bratton, Donna L.
    Henson, Peter M.
    Janssen, William J.
    Jakubzick, Claudia V.
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2017, 57 (01) : 66 - 76
  • [9] A critical role for microglia in maintaining vascular integrity in the hypoxic spinal cord
    Halder, Sebok K.
    Milner, Richard
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (51) : 26029 - 26037
  • [10] Microglia Are Irrelevant for Neuronal Degeneration and Axon Regeneration after Acute Injury
    Hilla, Alexander M.
    Diekmann, Heike
    Fischer, Dietmar
    [J]. JOURNAL OF NEUROSCIENCE, 2017, 37 (25) : 6113 - 6124
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