부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jaut.2007.10.003 Byline: Jorge Allina (a), Carmen M. Stanca (a), John Garber (a), Bin Hu (a), Catherine Sautes-Fridman (b), Nancy Bach (a), Joseph A. Odin (a) Abbreviations: PBC, primary biliary cirrhosis; HSG, human salivary gland epithelial cells; UV-B, ultraviolet B light; HI-FBS, heat-inactivated fetal bovine serum; MDM, monocyte derived macrophage; MRS, Mayo Risk Score; CFSE, carboxyfluoroscein succinimidyl ester; NHS, normal human serum; HDL, high density lipoprotein; PI, propidium iodide Abstract: Primary biliary cirrhosis is characterized by chronic hepatic inflammation and immune mediated apoptosis of bile duct epithelial cells. Delayed macrophage phagocytosis of opsonized apoptotic cells, noted in other autoimmune diseases, may promote inflammation. Recent studies suggest serum anti-CD16 autoantibodies contribute to impaired macrophage phagocytosis by blocking complement receptor 3 (CR3) signaling via CD16. Therefore, serum anti-CD16 levels and the ability of monocyte derived macrophages from individuals with PBC to phagocytosis apoptotic cells were compared to controls. The mean level of anti-CD16 IgM autoantibodies (0.86[+ or -]0.62 v. 0.35[+ or -]0.22, respectively, p =0.031) was increased in PBC compared to control sera, and mean PBC phagocytosis of opsonized apoptotic cells was significantly decreased compared to controls (23.9[+ or -]12.2% v. 43.9[+ or -]14.4%, respectively, p =0.020). However, PBC phagocytosis of opsonized apoptotic cells was not significantly affected by the presence or absence of autologous serum (20.8[+ or -]13.5% v. 23.9[+ or -]12.2%, respectively, p =0.560). PBC phagocytosis of opsonized apoptotic cells inversely correlated with CD16 (and CR3) expression levels on Day 5 after culture in the presence or absence of autologous serum (r =-0.546, p =0.033 and r =-0.519, p =0.042, respectively). Phagocytosis of non-opsonized apoptotic cells did not correlate with CD16 or CR3 expression (p 0.050). In conclusion, PBC macrophage phagocytosis of opsonized apoptotic cells is impaired, irrespective of serum factors and may increase hepatic inflammation. Author Affiliation: (a) Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA (b) Laboratory of Cellular and Clinical Immunology, INSERM Unit 255, Curie Institute, 75005 Paris, France Article History: Received 21 June 2007; Revised 10 October 2007; Accepted 10 October 2007