title: Expression and distribution of immunoglobulin G in the normal liver, hepatocarcinoma and postpartial hepatectomy liver.
abstract: The liver has the extraordinary properties of regeneration and immune tolerance; however, the mechanisms governing these abilities are poorly understood. To address these questions, we examined the possible expression of immunoglobulins in the human and rat liver and the relationship of IgG expression to hepatocyte proliferation, metastasis, apoptosis and immune tolerance. Immunohistochemistry, in situ hybridization, laser-guided microdissection and reverse transcription-PCR were performed to examine the expression of IgG in normal human and rat liver, severe combined immunodeficient mouse (SCID) liver and human liver cancers and corresponding cell lines. Small interfering RNA (siRNA) was transfected into cultured hepatocarcinoma cells to downregulate the expression of IgG heavy chain genes. Cell proliferation and apoptosis were assayed with flow cytometry. Cell metastasis was assayed with a Transwell cell assay. Partial hepatectomy (70%) was performed in rats to examine the relationship between hepatocyte IgG and hepatocyte proliferation. IgG, together with essential enzymes for its synthesis, were expressed in the cytoplasm of hepatocytes of normal adult human and hepatoma patients and rat livers, SCID mouse liver and BRL-3A, L-02 and HepG-2 cell lines. Downregulation of IgG inhibited cell proliferation and metastasis and promoted apoptosis. Postsurgery livers expressed significantly more IgG than the livers before surgery and decreased to the original levels when hepatocytes stopped regeneration. IgA and IgM but not IgD and IgE were also positive in hepatocytes. Our findings demonstrate that normal and malignant hepatocytes are capable of synthesizing immunoglobulin, which has important roles in hepatocyte proliferation, apoptosis and cancer growth with profound clinical implications.
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.affiliation: 1] Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China [2] Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Su
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Luo
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Christine
authors.initials: C
authors.lastname: Korteweg
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Zhengshan
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Xingmu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Yan
authors.affiliation: Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 1] Provincial Key Laboratory of Infectious Disease and Immunopathology, Department of Pathology, Shantou University Medical College, Shantou, China [2] Department of Pathology, School of Basic Medical Sciences, Peking University, Beijing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D015536:Down-Regulation; D056945:Hep G2 Cells; D006498:Hepatectomy; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D008114:Liver Neoplasms, Experimental / Q000276:immunology*; D008115:Liver Regeneration / Q000276:immunology*; D008297:Male; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D017207:Rats, Sprague-Dawley
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012333:RNA, Messenger; D034741:RNA, Small Interfering