title: Attenuated phagocytosis of secondary necrotic neutrophils by macrophages in aged and SMP30 knockout mice.
abstract: OBJECTIVE
  Secondary necrotic cells generated in vivo induce inflammatory responses; for example, the production of macrophage inflammatory protein-2 (MIP-2) and subsequent infiltration of neutrophils. The aim of the present study was to elucidate the effect of aging on the phagocytosis of secondary necrotic cells and the inflammatory responses by using either wild-type (WT) young mice, WT aged mice or senescence-accelerated mice (SMP30(-/-) mice).
  
  
  METHODS
  The phagocytosis of secondary necrotic neutrophils with resident macrophage from either WT young mice, WT aged mice or SMP30(-/-) mice was examined by coculturing macrophages with secondary necrotic neutrophils in vitro. To investigate the inflammatory response induced by secondary necrotic cells, time-dependent infiltration of neutrophils and production of MIP-2 were determined in the peritoneal cavity on the injection of secondary necrotic cells.
  
  
  RESULTS
  The phagocytosis of secondary necrotic cells by macrophages from WT aged and SMP30(-/-) mice was significantly reduced as compared with that by macrophages from WT young mice. On peritoneal injection of secondary necrotic cells, the peak time of neutrophil infiltration was earlier in SMP30(-/-) mice than in WT young mice. The number of neutrophils in SMP30(-/-) mice at the peak time was also greater than that in WT young mice.
  
  
  CONCLUSIONS
  Our findings showed that the phagocytosis of secondary necrotic cells was attenuated in aged mice and SMP30(-/-) mice, and that the MIP-2 production was enhanced and subsequently neutrophil infiltration was exaggerated on peritoneal injection of secondary necrotic cells into those mice.
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, Chiba.
authors.forename: Rei
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, Chiba.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Totsuka
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, Chiba.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Biomolecular Science, Faculty of Science, Toho University, Chiba.
authors.forename: Kisaburo
authors.initials: K
authors.lastname: Nagata
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology*; D010529:Peritoneal Cavity / Q000473:pathology*; D010587:Phagocytosis / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C513324:Rgn protein, mouse
keywords: aging; apoptosis; chemokines; inflammation; macrophages