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Cell Immunol. 2016 Jun-Jul;304-305:44-8. doi: 10.1016/j.cellimm.2016.03.001. Epub 2016 Mar 3.

Skewing of peritoneal resident macrophages toward M1-like is involved in enhancement of inflammatory responses induced by secondary necrotic neutrophils in aged mice.

Author information

1
Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
2
Aging Regulation, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
3
Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan. Electronic address: nagata@biomol.sci.toho-u.ac.jp.

Abstract

Secondary necrotic cells, which are generated if apoptotic cells are incompletely cleared, induce severe inflammatory responses involving MIP-2 production and subsequent neutrophil infiltration. Recently, we showed that the phagocytic capacity of peritoneal resident macrophages from wild type (WT) aged mice as well as SMP30(-/-) mice fed a VC-limited diet as to secondary necrotic cells was reduced as compared with that in young mice, and that the inflammatory responses induced were stronger than those in young mice, presumably because of the delay in removal of secondary necrotic cells in aged mice. In this study, we investigated why MIP-2 production was increased in aged mice upon injection of secondary necrotic cells and why the phagocytic capacity of peritoneal resident macrophages from aged mice was reduced. When cocultured with secondary necrotic cells, the peritoneal resident macrophages from both types of aged mice significantly produced MIP-2 even in the absence of IFN-γ, whereas MIP-2 production by macrophages from WT young mice required IFN-γ. The peritoneal resident macrophages from both types of aged mice expressed CD40, a M1 macrophage marker, as in the case of M1 macrophages, which were obtained by treatment of macrophages from WT young mice with IFN-γ and LPS. Furthermore, M1 macrophages exhibited less phagocytic capacity as to secondary necrotic cells than non-treated macrophages. These results suggest that the phenotype of peritoneal resident macrophages is skewed toward M1-like in aged mice and that such skewing toward M1-like is involved in enhancement of inflammatory responses induced by secondary necrotic neutrophils in aged mice.

KEYWORDS:

Aging; Chemokines; Inflammation; M1 macrophages; Secondary necrosis

PMID:
26965995
DOI:
10.1016/j.cellimm.2016.03.001
[Indexed for MEDLINE]

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