Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.

In the murine liver, there are two major macrophage populations, namely resident Kupffer cells (resKCs) with phagocytic activity and recruited macrophages (recMφs) with cytokine-producing capacity. This study was performed to clarify the functional differences between these two populations, focusing...

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Autores principales:	Takuya Ishikiriyama, Hiroyuki Nakashima, Kaori Endo-Umeda, Masahiro Nakashima, Seigo Ito, Manabu Kinoshita, Masami Ikarashi, Makoto Makishima, Shuhji Seki
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d93a9c9b10d947b2936efcaf3b21a4c4
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spelling	oai:doaj.org-article:d93a9c9b10d947b2936efcaf3b21a4c42021-12-02T20:04:53ZContrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.1932-620310.1371/journal.pone.0254886https://doaj.org/article/d93a9c9b10d947b2936efcaf3b21a4c42021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0254886https://doaj.org/toc/1932-6203In the murine liver, there are two major macrophage populations, namely resident Kupffer cells (resKCs) with phagocytic activity and recruited macrophages (recMφs) with cytokine-producing capacity. This study was performed to clarify the functional differences between these two populations, focusing on their susceptibility to radiation and response to stimulation via liver X receptors (LXRs), which are implicated in cholesterol metabolism and immune regulation. Liver mononuclear cells (MNCs) were obtained from C57BL/6 (WT) mice with or without 2 Gy irradiation, and the phagocytic activity against Escherichia coli (E. coli) as well as TNF-α production were compared between the two macrophage populations. To assess LXR functions, phagocytosis, TNF-α production, and endocytosis of acetylated low-density lipoprotein (LDL) were compared after synthetic LXR ligand stimulation. Furthermore, LXRα/β knockout (KO) mice and LXRα KO mice were compared with WT mice. Irradiation decreased intracellular TNF-α production by recMφs but did not affect the phagocytic activity of resKCs. In vitro LXR stimulation enhanced E. coli phagocytosis by resKCs but decreased E. coli-stimulated TNF-α production by recMφs. Phagocytic activity and acetylated LDL endocytosis were decreased in both LXRα/β KO mice and LXRα KO mice, with serum TNF-α levels after E. coli injection in the former being higher than those in WT mice. In conclusion, resKCs and recMφs exhibited different functional features in response to radiation and LXR stimulation, highlighting their distinct roles liver immunity and lipid metabolism.Takuya IshikiriyamaHiroyuki NakashimaKaori Endo-UmedaMasahiro NakashimaSeigo ItoManabu KinoshitaMasami IkarashiMakoto MakishimaShuhji SekiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0254886 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Takuya Ishikiriyama Hiroyuki Nakashima Kaori Endo-Umeda Masahiro Nakashima Seigo Ito Manabu Kinoshita Masami Ikarashi Makoto Makishima Shuhji Seki Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.
description	In the murine liver, there are two major macrophage populations, namely resident Kupffer cells (resKCs) with phagocytic activity and recruited macrophages (recMφs) with cytokine-producing capacity. This study was performed to clarify the functional differences between these two populations, focusing on their susceptibility to radiation and response to stimulation via liver X receptors (LXRs), which are implicated in cholesterol metabolism and immune regulation. Liver mononuclear cells (MNCs) were obtained from C57BL/6 (WT) mice with or without 2 Gy irradiation, and the phagocytic activity against Escherichia coli (E. coli) as well as TNF-α production were compared between the two macrophage populations. To assess LXR functions, phagocytosis, TNF-α production, and endocytosis of acetylated low-density lipoprotein (LDL) were compared after synthetic LXR ligand stimulation. Furthermore, LXRα/β knockout (KO) mice and LXRα KO mice were compared with WT mice. Irradiation decreased intracellular TNF-α production by recMφs but did not affect the phagocytic activity of resKCs. In vitro LXR stimulation enhanced E. coli phagocytosis by resKCs but decreased E. coli-stimulated TNF-α production by recMφs. Phagocytic activity and acetylated LDL endocytosis were decreased in both LXRα/β KO mice and LXRα KO mice, with serum TNF-α levels after E. coli injection in the former being higher than those in WT mice. In conclusion, resKCs and recMφs exhibited different functional features in response to radiation and LXR stimulation, highlighting their distinct roles liver immunity and lipid metabolism.
format	article
author	Takuya Ishikiriyama Hiroyuki Nakashima Kaori Endo-Umeda Masahiro Nakashima Seigo Ito Manabu Kinoshita Masami Ikarashi Makoto Makishima Shuhji Seki
author_facet	Takuya Ishikiriyama Hiroyuki Nakashima Kaori Endo-Umeda Masahiro Nakashima Seigo Ito Manabu Kinoshita Masami Ikarashi Makoto Makishima Shuhji Seki
author_sort	Takuya Ishikiriyama
title	Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.
title_short	Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.
title_full	Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.
title_fullStr	Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.
title_full_unstemmed	Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.
title_sort	contrasting functional responses of resident kupffer cells and recruited liver macrophages to irradiation and liver x receptor stimulation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d93a9c9b10d947b2936efcaf3b21a4c4
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Contrasting functional responses of resident Kupffer cells and recruited liver macrophages to irradiation and liver X receptor stimulation.

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