title: Skewing of peritoneal resident macrophages toward M1-like is involved in enhancement of inflammatory responses induced by secondary necrotic neutrophils in aged mice.
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.
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Aging Regulation, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishigami
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, Funabashi, Chiba, Japan. Electronic address: nagata@biomol.sci.toho-u.ac.jp.
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics; D002454:Cell Differentiation; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism*; D018920:Coculture Techniques; D057899:Cytophagocytosis; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008070:Lipopolysaccharides / Q000378:metabolism; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology*; D010641:Phenotype
chemical_list: D019013:CD40 Antigens; D002135:Calcium-Binding Proteins; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; C513324:Rgn protein, mouse; D007371:Interferon-gamma
keywords: Aging; Chemokines; Inflammation; M1 macrophages; Secondary necrosis