title: Cross-reactivity of Antibodies Directed to the Gram-Negative Bacterium Neisseria gonorrhoeae With Heat Shock Protein 60 and ATP-Binding Protein Correlates to Reduced Mitochondrial Activity in HIBCPP Choroid Plexus Papilloma Cells.
abstract: Antibacterial antibodies can cause neurologic side-effects by cross-reactivity with cellular antigens. Here we investigated interactions of antibodies to Neisseria gonorrhoeae (α-NG) - maternal infections by which increases the offspring's risk for later psychosis-with HIBCPP cells, a cell culture model of choroid plexus epithelium. Immunocytochemistry and Western blotting with α-NG, revealed organelle-like intracellular staining in HIBCPP cells, and labelling of several immunoreactive bands in cellular protein. Two-dimensional Western blotting revealed several immunopositive spots, most prominent of which were identified by mass spectrometry as mitochondrially localized proteins heat shock protein 60 (Hsp60) and ATP-binding protein β-subunit (ATPB). Similarly α-NG interacted with commercial samples of these proteins as revealed by Western blotting. Three alternative methods (JC-1, Janus green and MTT staining) revealed α-NG to cause in HIBCPP cells a significant decrease in mitochondrial activity, which could be reverted by neuroleptic drugs. Immunoreactivity of α-NG with choroid plexus epithelium in human post mortem samples suggests in vivo relevance of these findings. Finally, distinctly different staining patterns of antibodies against Neisseria meningitidis (α-NM), confirmed antibody specificity. To our knowledge this is the first report that α-NG cross-reactivity with Hsp60 and ATPB impairs mitochondrial activity in choroid plexus epithelial cells, pathogenetic relevance of which needs further clarification.
authors.affiliation: Institute for Neuroanatomy, University Medicine Göttingen (UMG), Kreuzbergring 36, 37075, Göttingen, Federal Republic of Germany, breuss@gwdg.de.
authors.forename: B
authors.initials: B
authors.lastname: Reuss
authors.forename: H
authors.initials: H
authors.lastname: Schroten
authors.forename: H
authors.initials: H
authors.lastname: Ishikawa
authors.forename: A R
authors.initials: AR
authors.lastname: Asif
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology*; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000276:immunology*; D003429:Cross Reactions; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000276:immunology*; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology
chemical_list: C506526:ATP5F1B protein, human; D000907:Antibodies, Bacterial; D018834:Chaperonin 60; D025261:Mitochondrial Proton-Translocating ATPases