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

Kupffer cells consist of resident CD32/CD68+ cells and recruited CD11b+ cells, which engage in bactericidal and antitumor immunity. 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...

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Bibliographic Details
Published in:Journal of leukocyte biology 2013-12, Vol.94 (6), p.1325-1336
Main Authors: Ikarashi, Masami, Nakashima, Hiroyuki, Kinoshita, Manabu, Sato, Atsushi, Nakashima, Masahiro, Miyazaki, Hiromi, Nishiyama, Kiyoshi, Yamamoto, Junji, Seki, Shuhji
Format: Article
Language:English
Subjects:
Aged
Animals
Antigens, CD - immunology
Antigens, CD - metabolism
antitumor immunity
bacterial infection
CD32
CD68
Cell Line, Tumor
Female
Humans
Kupffer Cells - classification
Kupffer Cells - cytology
Kupffer Cells - immunology
Kupffer Cells - metabolism
Liver Neoplasms - immunology
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Male
Mice
Middle Aged
Staphylococcus aureus - immunology
Staphylococcus aureus - metabolism
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Summary:Kupffer cells consist of resident CD32/CD68+ cells and recruited CD11b+ cells, which engage in bactericidal and antitumor immunity. 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.
ISSN:0741-5400
1938-3673
DOI:10.1189/jlb.0313144