CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages
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 ch...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2020-09, Vol.117 (38), p.23336-23338 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Lei, Fengyang Cui, Naiwen Zhou, Chengxin Chodosh, James |
| description | 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. |
| doi_str_mv | 10.1073/pnas.1922788117 |
| format | Article |
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| subjects | Biological Sciences Bone marrow BRIEF REPORT Central nervous system Colony-stimulating factor Depletion Endotoxins Hematopoiesis Immune system Interleukins Long bone Macrophage colony-stimulating factor Macrophages Microglia Monocytes Peritoneum Phagocytosis Spleen |
| title | CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages |
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