title: Distinct development and functions of resident and recruited liver Kupffer cells/macrophages.
abstract: Although mouse liver F4/80(+) Kupffer cells consist of cytokine-producing CD11b(+) cells and phagocytic CD68(+) cells, an undefined CD11b(-) CD68(-) subset (30%) also exists. We herein demonstrate a more fundamental classification by adding CD32 (FcγRII), which covers most liver F4/80(+) cells and the distinct functions of them. Among the F4/80(+) cells, 50%, 40%, and 30% of cells were CD32(+), CD68(+), and CD11b(+), respectively, and one-half of the CD68(+) cells coexpressed CD32. CD68(+) and CD32(+) cells, but not CD11b(+) cells, expressed a phagocytosis-related CRIg. Gy (6) irradiation depleted liver CD11b(+) cells and those in the spleen, bone marrow, and peripheral blood but not liver CD32/CD68(+) cells. Transfer of bone marrow cells into the irradiated mice reconstituted liver CD11b(+) cells. Conversely, clodronate pretreatment depleted only liver CD32/CD68(+) cells but not liver CD11b(+) cells and peripheral blood or spleen CD11b(+) monocytes/macrophages. Moreover, the CD32(+) cells might be precursors of CD68(+) cells, as a large proportion of CD32(+) cells expressed the c-kit (CD117), and CD34 and CD32(+) cells acquired CD68 immediately after bacteria administration. CD32/CD68(+) cells, but not CD11b(+) cells, expressed resident macrophage-specific MerTK and CD64 (FcγRI). Challenge with Staphylococcus aureus or liver metastatic EL-4 tumor cells indicated that the CD68(+) subset is engaged in systemic bactericidal activity, whereas the CD11b(+) subset is pivotal for liver antitumor immunity. Human liver CD14(+) Kupffer cells could also be classified into three similar subsets. These results suggest that liver CD68(+) Kupffer cells and CD11b(+) Kupffer cells/macrophages are developmentally and functionally distinct subsets.
authors: 1.National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513 Japan. btraums@ndmc.ac.jp.
authors: Masami
authors: M
authors: Ikarashi
authors: Hiroyuki
authors: H
authors: Nakashima
authors: Manabu
authors: M
authors: Kinoshita
authors: Atsushi
authors: A
authors: Sato
authors: Masahiro
authors: M
authors: Nakashima
authors: Hiromi
authors: H
authors: Miyazaki
authors: Kiyoshi
authors: K
authors: Nishiyama
authors: Junji
authors: J
authors: Yamamoto
authors: Shuhji
authors: S
authors: Seki
mesh_terms: D000368:Aged; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007728:Kupffer Cells / Q000145:classification / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D013211:Staphylococcus aureus / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD
keywords: CD32; CD68; antitumor immunity; bacterial infection