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

被引：198

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

页码：23336 / 23338

页数：3

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