Giovanni Sitia1#*, Matteo Iannacone1,2#*, Roberto Aiolfi1, Masanori Isogawa3, Nico van Rooijen4, Cristina Scozzesi5, Marco E. Bianchi6,7, Ulrich H. von Andrian2, Francis V. Chisari3, Luca G. Guidotti1,3*
1 Division of Immunology, Transplantation and Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy, 2 Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Immunology & Microbial Sciences, The Scripps Research Institute, La Jolla, California, United States of America, 4 Department of Molecular Cell Biology, Free University Medical Center, Amsterdam, The Netherlands, 5 DiaPro Diagnostic Bioprobes, Milan, Italy, 6 Vita-Salute San Raffaele University, Milan, Italy, 7 Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy
Abstract TopKupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology.枯否细胞,是在衬里肝血窦壁形成的网状内皮系统(又名:单核吞噬细胞系统)的一部分,位于专门的巨噬细胞
Kupffer细胞是全身单核-吞噬细胞系统的重要组成部分, 也是肝脏防御系统主要成员, 在全身和肝脏疾病发生发展中起到重要作用
作 者 郭芳(桂林医学院附属医院,广西桂林,541001);李美琼(桂林医学院附属医院,广西桂林,541001);陈秋月(桂林医学院附属医院,广西桂林,541001);林静(桂林医学院附属医院,广西桂林,541001);侯巧燕(桂林医学院附属医院,广西桂林,541001);曾思恩(桂林医学院附属医院,广西桂林,541001);
目的 研究HBsAg阳性患者HBcAg表达与肝组织中T、B淋巴细胞、NK细胞、Kupffer细胞数量等临床指标变化的关系.方法 选取50例HBsAg阳性表达的患者肝组织及23例肝血管瘤患者瘤旁正常肝组织,分别进行CD3、CD57、CD20、CD68及HBcAg免疫组织化学 染色;用病理图像分析仪测量每例患者肝组织和正常肝组织每平方微米面积阳性细胞数.结果 HBsAg阳性表达的患者肝组织中T淋巴细胞、B淋巴细胞、NK细胞和Kupffer细胞数量明显多于正常肝组织,以T淋巴细胞数量增加最为显著 (P<0.05),HBcAg阳性表达组与HBcAg阴性表达组肝组织中T淋巴细胞、B淋巴细胞、NK细胞和Kupffer细胞数量变化无统计学意义(P>0.05).HBcAg阳性表达组比HBcAg阴性表达组外周血的AFP、ALT含量高(P均<0.05),AST、GGT、ALP、白蛋白减少(P均<0.05),A/G比例降低(P<0.01).结论 各免疫细胞数量变化与膜型HBsAg的表达有关,与核型HBcAg表达无关;但核型HBcAg的表达与各临床指标的改变密切相关.
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