title: Alterations of serum protein N-glycosylation in two mouse models of chronic liver disease are hepatocyte and not B cell driven.
abstract: N-glycosylation of immunoglobulin G (IgG) has an important impact on the modification of the total serum N-glycome in chronic liver patients. Our aim was to determine the role and magnitude of the alterations in which hepatocytes and B cells are involved in two mouse models of chronic liver disease. Common bile duct ligation (CBDL) and subcutaneous injections with CCl(4) were induced in B cell-deficient and wild-type (WT) mice. IgG depletion was performed with beads covered with protein A/G and the depletions were evaluated by SDS-PAGE and Western blot analysis. N-glycan analysis was performed by improved DSA-FACE technology. Structural analysis of the mouse serum N-glycans was performed by exoglycosidase digests and MALDI-TOF mass spectrometry of permethylated glycans. The alterations seen in B cell-deficient mice closely resembled the alterations in WT mice, in both the CBDL and the CCl(4) models. N-glycan analysis of the IgG fraction in both mouse models revealed different changes compared with humans. Overall, the impact of IgG glycosylation on total serum glycosylation was marginal. Interestingly, the amount of fibrosis present in CBDL B cell-deficient mice was significantly increased compared with CBDL WT mice, whereas the opposite was true for the CCl(4) model as determined by Sirius red staining. However, this had no major effect on the alteration of N-glycosylation of serum proteins. Alterations of total serum N-glycome in mouse models of chronic liver disease are hepatocyte-driven. Undergalactosylation of IgG is not present in mouse models of chronic liver disease.
authors.affiliation: Dept. of Hepatology and Gastroenterology, Ghent Univ. Hospital, Belgium.
authors.forename: Bram
authors.initials: B
authors.lastname: Blomme
authors.forename: Christophe
authors.initials: C
authors.lastname: Van Steenkiste
authors.forename: Paola
authors.initials: P
authors.lastname: Grassi
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Haslam
authors.forename: Anne
authors.initials: A
authors.lastname: Dell
authors.forename: Nico
authors.initials: N
authors.lastname: Callewaert
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001652:Bile Ducts / Q000502:physiology; D001798:Blood Proteins / Q000378:metabolism*; D001835:Body Weight / Q000502:physiology; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism* / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D022781:Hepatocytes / Q000502:physiology*; D007074:Immunoglobulin G / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000502:physiology; D008297:Male; D008745:Methylation; D051379:Mice; D057507:Mice, 129 Strain; D009929:Organ Size / Q000502:physiology; D011134:Polysaccharides / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000093422:Glycated Serum Proteins
chemical_list: D001798:Blood Proteins; D006023:Glycoproteins; D007074:Immunoglobulin G; D011134:Polysaccharides; D000093422:Glycated Serum Proteins