title: A deficiency in the in vivo clearance of apoptotic cells is a feature of the NOD mouse.
abstract: Deficiencies in apoptotic cell clearance have been linked to autoimmunity. Here we examined the time-course of peritoneal macrophage phagocytosis of dying cells following the direct injection of apoptotic thymocytes into the peritoneum of NOD mice and BALB/c controls. Macrophages from NOD mice demonstrated a profound defect in the phagocytosis of apoptotic thymocytes as compared to control macrophages. Nonobese diabetic mice also demonstrated a decrease in the clearance of apoptotic cell loads following an apoptotic stimulus to thymocytes (dexamethasone) when compared to BALB/c or NOR controls. Further, NOD mice demonstrated an increase in apoptotic cell load following an apoptotic stimulus to keratinocytes (ultraviolet light, UVB) when compared to control strains. Animals deficient in macrophage phagocytosis of apoptotic debris often manifest an autoimmune phenotype characterized by the production of antinuclear autoantibodies (ANA). We determined whether increased apoptotic cell loads (through repeated exposure to UVB irradiation) could accelerate such autoimmune phenomena in young NOD mice. Following repeated UVB irradiation, NOD mice, but not BALB/c or NOR controls, developed ANA. We propose that abnormalities in apoptotic cell clearance by macrophages predispose NOD mice to autoimmunity.
authors.affiliation: University of Technology, Sydney, Australia.
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: O'Brien
authors.forename: Xuan
authors.initials: X
authors.lastname: Geng
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Orteu
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Huang
authors.forename: Mehran
authors.initials: M
authors.lastname: Ghoreishi
authors.forename: YiQun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jason A
authors.initials: JA
authors.lastname: Bush
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Diane T
authors.initials: DT
authors.lastname: Finegood
authors.forename: Jan Peter
authors.initials: JP
authors.lastname: Dutz
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology / Q000528:radiation effects; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D010587:Phagocytosis / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014466:Ultraviolet Rays
chemical_list: D000974:Antibodies, Antinuclear; D003907:Dexamethasone