CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages.
Animals
Antigens, CD
/ genetics
Antigens, Differentiation, Myelomonocytic
/ genetics
Female
Hematopoiesis
/ drug effects
Interleukin-1beta
/ genetics
Macrophages
/ drug effects
Male
Mice
Mice, Inbred C57BL
Microglia
/ drug effects
Organic Chemicals
/ pharmacology
Phagocytosis
/ drug effects
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
/ antagonists & inhibitors
Species Specificity
CNS
CSF1R
hematopoiesis
macrophages
microglia
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
22 09 2020
22 09 2020
Historique:
pubmed:
10
9
2020
medline:
11
11
2020
entrez:
9
9
2020
Statut:
ppublish
Résumé
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 1β, 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.
Identifiants
pubmed: 32900927
pii: 1922788117
doi: 10.1073/pnas.1922788117
pmc: PMC7519218
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, Myelomonocytic
0
CD68 antigen, human
0
Csf1r protein, mouse
0
Interleukin-1beta
0
Organic Chemicals
0
PLX5622
0
Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
23336-23338Subventions
Organisme : NEI NIH HHS
ID : P30 EY003790
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY014104
Pays : United States
Organisme : NEI NIH HHS
ID : R21 EY023079
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2020 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
J Neuroinflammation. 2015 Aug 01;12:139
pubmed: 26232154
Neuron. 2014 Apr 16;82(2):380-97
pubmed: 24742461
Proc Natl Acad Sci U S A. 2019 Dec 17;116(51):26029-26037
pubmed: 31772011
J Neuroinflammation. 2018 Dec 12;15(1):340
pubmed: 30541565
Nat Immunol. 2012 Nov;13(11):1118-28
pubmed: 23023392
Immunity. 2018 Aug 21;49(2):312-325.e5
pubmed: 30076102
J Neurosci. 2017 Jun 21;37(25):6113-6124
pubmed: 28539419
Am J Respir Cell Mol Biol. 2017 Jul;57(1):66-76
pubmed: 28257233
Cancer Res. 2014 Jan 1;74(1):153-161
pubmed: 24247719
Science. 2019 Mar 15;363(6432):
pubmed: 30872492
Immunity. 2016 Mar 15;44(3):450-462
pubmed: 26982353
Exp Neurol. 2014 Apr;254:109-20
pubmed: 24468477
J Neuroinflammation. 2018 Dec 15;15(1):344
pubmed: 30553275
Nat Commun. 2016 Jun 13;7:ncomms11852
pubmed: 27292029
Brain Res. 2019 Oct 15;1721:146328
pubmed: 31295468
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):E11359-E11368
pubmed: 30442669
Am J Pathol. 2018 Jul;188(7):1580-1596
pubmed: 29630857
J Immunol. 2019 Jan 15;202(2):539-549
pubmed: 30541880
Nat Commun. 2019 Jan 31;10(1):518
pubmed: 30705270