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J Leukoc Biol. 2013 Dec;94(6):1325-36. doi: 10.1189/jlb.0313144. Epub 2013 Aug 20.

Distinct development and functions of resident and recruited liver Kupffer cells/macrophages.

Author information

  • 11.National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513 Japan. btraums@ndmc.ac.jp.

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.

KEYWORDS:

CD32; CD68; antitumor immunity; bacterial infection

PMID:
23964119
[PubMed - indexed for MEDLINE]
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