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 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.
['Lei|Fengyang|F|0000-0002-9169-8314', 'Cui|Naiwen|N|0000-0002-7240-822X', 'Zhou|Chengxin|C|0000-0003-3215-068X', 'Chodosh|James|J|0000-0002-7463-1599', 'Vavvas|Demetrios G|DG|0000-0002-8622-6478', 'Paschalis|Eleftherios I|EI|0000-0002-4544-4452']
D000818:Animals D015703:Antigens, CD D015214:Antigens, Differentiation, Myelomonocytic D005260:Female D006410:Hematopoiesis D053583:Interleukin-1beta D008264:Macrophages D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D017628:Microglia D009930:Organic Chemicals D010587:Phagocytosis D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor D013045:Species Specificity
CSF1R microglia hematopoiesis macrophages CNS