title: Phagocytosis of apoptotic cells by macrophages from NOD mice is reduced.
abstract: Macrophages limit inflammatory responses by clearing apoptotic cells. Deficiencies in apoptotic cell phagocytosis have been linked to autoimmunity. In this study, we determined the efficiency with which macrophages from diabetes-prone NOD and diabetes-resistant NOR, Idd5, Balb/c, and C57BL/6 mice phagocytose apoptotic thymocytes and NIT-1 insulinoma cells. Peritoneal and bone marrow-derived macrophages from NOD mice engulfed fewer apoptotic thymocytes than macrophages from Balb/c mice (P < 0.05). Peritoneal macrophages from NOR and Idd5 NOD congenic mice were more proficient at engulfment than their NOD counterparts. Annexin V blockade diminished apoptotic thymocyte clearance and heat-labile serum factors augmented clearance. Binding of apoptotic thymocytes to NOD macrophages was also reduced, suggesting that the deficiency in phagocytosis may be partly attributable to a recognition defect. Peritoneal macrophages from female Balb/c and NOD mice were equally efficient in the engulfment of microspheres, suggesting that the phagocytic deficiency observed in NOD mice was specific for apoptotic cells. In summary, we have demonstrated a deficiency in phagocytic function of macrophages from NOD mice. Normal and diabetes-prone neonatal rodents have a wave of beta-cell apoptosis coincident with the onset of target organ inflammation. A constitutive defect in the clearance of apoptotic beta-cells may be contributory to the initiation of autoimmunity.
authors.affiliation: Diabetes Research Laboratory, Department of Kinesiology, Simon Fraser University, Burnaby, British Columbia, Canada.
authors.forename: Bronwyn A
authors.initials: BA
authors.lastname: O'Brien
authors.forename: Yongqian
authors.initials: Y
authors.lastname: Huang
authors.forename: Xuan
authors.initials: X
authors.lastname: Geng
authors.forename: Jan P
authors.initials: JP
authors.lastname: Dutz
authors.forename: Diane T
authors.initials: DT
authors.lastname: Finegood
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D020287:In Situ Nick-End Labeling; D007340:Insulinoma; D008264:Macrophages / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010190:Pancreatic Neoplasms; D010587:Phagocytosis / Q000502:physiology*; D012727:Sex Characteristics; D013045:Species Specificity; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology; D014407:Tumor Cells, Cultured