title: Vascular-resident CD169-positive monocytes and macrophages control neutrophil accumulation in the kidney with ischemia-reperfusion injury.
abstract: Monocytes and kidney-resident macrophages are considered to be involved in the pathogenesis of renal ischemia-reperfusion injury (IRI). Several subsets of monocytes and macrophages are localized in the injured tissue, but the pathologic roles of these cells are not fully understood. Here, we show that CD169(+) monocytes and macrophages have a critical role in preventing excessive inflammation in IRI by downregulating intercellular adhesion molecule-1 (ICAM-1) expression on vascular endothelial cells. Mice depleted of CD169(+) cells showed enhanced endothelial ICAM-1 expression and developed irreversible renal damage associated with infiltration of a large number of neutrophils. The perivascular localization of CD169(+) monocytes and macrophages indicated direct interaction with blood vessels, and coculture experiments showed that the direct interaction of CD169(+) cell-depleted peripheral blood leukocytes augments the expression levels of ICAM-1 on endothelial cells. Notably, the transfer of Ly6C(lo) monocytes into CD169(+) cell-depleted mice rescued the mice from lethal renal injury and normalized renal ICAM-1 expression levels, indicating that the Ly6C(lo) subset of CD169(+) monocytes has a major role in the regulation of inflammation. Our findings highlight the previously unknown role of CD169(+) monocytes and macrophages in the maintenance of vascular homeostasis and provide new approaches to the treatment of renal IRI.
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan;
authors.forename: Kazunori
authors.initials: K
authors.lastname: Karasawa
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; Japan Science and Technology Agency, PRESTO, Saitama, Japan; and.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Asano
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Moriyama
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ushiki
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;
authors.forename: Misa
authors.initials: M
authors.lastname: Monya
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;
authors.forename: Mayumi
authors.initials: M
authors.lastname: Iida
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;
authors.forename: Erika
authors.initials: E
authors.lastname: Kuboki
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan;
authors.forename: Keiko
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Medicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan;
authors.forename: Kosaku
authors.initials: K
authors.lastname: Nitta
authors.affiliation: Laboratory of Immune Regulation, School of Life Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; mtanaka@toyaku.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
mesh_terms: D058186:Acute Kidney Injury / Q000276:immunology*; D000818:Animals; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000502:physiology*; D015427:Reperfusion Injury / Q000276:immunology*; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000032:analysis*
chemical_list: D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse; D018799:Intercellular Adhesion Molecule-1
keywords: acute renal failure; immunology and pathology; ischemia-reperfusion; macrophages