title: Monocyte chemoattractant protein (MCP)-1 production via functionally reconstituted Fcalpha receptor (CD89) on glomerular mesangial cells.
abstract: BACKGROUND
  Fc alpha receptor (FcalphaR; CD89) is the receptor for Fc portion of IgA in various cells, and displays various immunological responses on binding. It is important to analyze the mesangial functions via FcalphaR in the pathogenesis of IgA nephropathy. However, it is still controversial whether FcalphaR is expressed on mesangial cells. To assess biological functions of FcalphaR on the mesangial cells, we established mesangial transfectants that expressed FcalphaR with or without FcRgamma chain that is a common signaling molecule of FcRs. The production of monocyte chemoattractant protein-1 (MCP-1) by mesangial cells is known to contribute to cellular infiltration into glomeruli and subsequent glomerular injuries.
  
  
  METHODS
  Murine mesangial cell lines (SV40 MES 13) were transfected with cDNA of the human FcalphaR. Furthermore, we co-transfected some of the FcalphaR transfectants with cDNA of human FcRgamma chain. The tyrosine phosphorylation of the intra-mesangial proteins after FcalphaR cross-linking was examined by immunoprecipitation. MCP-1 production from each transfectant stimulated with heat aggregated IgA was determined by sandwich ELISA.
  
  
  RESULTS
  Two kinds of mesangial transfectants stably expressed human FcalphaR with or without FcRgamma chain (FcalphaR(+), FcalphaR(+)/gamma(+)). Phosphorylation of FcRgamma chain and syk kinase was detected in FcalphaR(+) and FcalphaR(+)/gamma(+) cells, but not in untransfected cells. Aggregated IgA induced significantly higher MCP-1 production in FcalphaR(+)/gamma(+) than those in FcalphaR(+) or untransfected control.
  
  
  CONCLUSIONS
  Present study demonstrated that FcalphaR and FcRgamma chain could be reconstituted in mesangial cells and mediated MCP-1 production by aggregated IgA in a dose-dependent manner. Current data would argue that FcalphaR can be activated in mesangial cells through their own machinery, although underlying mechanisms for FcalphaR induction in mesangial cells remain unclear.
authors.affiliation: Department of Internal Medicine, Juntendo University School of Medicine, 2-1-1 Hongo, 113-8421 Tokyo, Japan, Bunkyo-ku.
authors.forename: T
authors.initials: T
authors.lastname: Tsuge
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Shimokawa
authors.forename: S
authors.initials: S
authors.lastname: Horikoshi
authors.forename: K
authors.initials: K
authors.lastname: Okumura
authors.forename: C
authors.initials: C
authors.lastname: Ra
authors.forename: Y
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D011961:Receptors, Fc / Q000378:metabolism*; D000072377:Syk Kinase; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018932:Chemokine CCL2; D004792:Enzyme Precursors; C036832:Fc(alpha) receptor; D047908:Intracellular Signaling Peptides and Proteins; D011961:Receptors, Fc; D014443:Tyrosine; D012313:RNA; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse