title: Alterations of cell adhesion molecules in human glomerular endothelial cells in response to nephritis-associated plasminogen receptor.
abstract: BACKGROUND
  Acute post-streptococcal glomerulonephritis (APSGN) is induced by glomerular deposition of nephritogenic streptococcal antigen-antibody complexes. Recently, a streptococcal antigen, nephritis-associated plasminogen receptor (NAPlr) was purified from ruptured streptococcal cell supernatants (RCS). However, the cellular and molecular mechanisms of NAPlr action on the glomerular vas culature are still unknown.
  
  
  METHODS
  Expression of cell adhesion molecules were measured by cellular ELISA (enzyme-linked immunosorbent assay), immunofluorescence microscopy and Western blot analysis.
  
  
  RESULTS
  RCS and NAPlr significantly decreased the PECAM-1 expression in human glomerular endothelial cells (HGECs) as compared to that in the control cells. Plasminogen treatment reversed the RCS or NAPlr-induced decrease of PECAM-1 expression and increase of MCP-1 expression. Immunofluorescent microscopy and Western blot analysis also showed that PECAM-1 expression in HGECs was downregulated upon treatment with RCS or NAPlr and this effect was reversed by plasminogen treatment. Furthermore, we found that tumor necrosis factor-alpha production in culture medium of HGECs was increased at the lower level when the culture system was treated with RCS.
  
  
  CONCLUSIONS
  RCS and NAPlr modulated PECAM-1 expression and MCP-1 production in HGECs, indicating the involvement of NAPlr in inflammatory cell accumulation in glomerular tufts and functional abnormality of glomerular microvasculature such as hyperpermeability.
authors.affiliation: Department of Cellular Physiology, Institute of Nephrology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
authors.forename: Fahima
authors.initials: F
authors.lastname: Khan
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamakami
authors.forename: Javed
authors.initials: J
authors.lastname: Mahmood
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Tamami
authors.initials: T
authors.lastname: Kikuchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumagai
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Morioka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yoshizawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Oite
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology / Q000502:physiology*; D002199:Capillary Permeability; D018932:Chemokine CCL2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D005921:Glomerulonephritis / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism*; D009393:Nephritis / Q000150:complications / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D013290:Streptococcal Infections / Q000150:complications; D013291:Streptococcus / Q000472:pathogenicity; D013297:Streptococcus pyogenes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011956:Receptors, Cell Surface; C517776:nephritis-associated plasminogen receptor, Streptococcus; D018799:Intercellular Adhesion Molecule-1