Distinct development and functions of resident and recruited liver Kupffer cells/macrophages. Issue 6 (20th August 2013)

• Record Type: Journal Article
• Authors: Ikarashi, Masami; Nakashima, Hiroyuki; Kinoshita, Manabu; Sato, Atsushi; Nakashima, Masahiro; Miyazaki, Hiromi; Nishiyama, Kiyoshi; Yamamoto, Junji; Seki, Shuhji
• Is Part Of: Journal of leukocyte biology. Volume 94:Issue 6(2013)
• Page Start: 1325
• Page End: 1336
• Publication Date: 2013-08-20
• Subjects: CD32 -- CD68 -- bacterial infection -- antitumor immunity; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.0313144
• Languages: English
• ISSNs: 0741-5400

Abstract

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