title: Macrophage impairment produced by Fc receptor gamma deficiency plays a principal role in the development of lipoprotein glomerulopathy in concert with apoE abnormalities.
abstract: BACKGROUND
  To obtain a clear understanding of the pathogenesis of lipoprotein glomerulopathy (LPG), we studied the role of the deficiency of Fc receptor gamma chain (FcRγ) for the development of LPG in concert with apolipoprotein E (apoE) abnormalities.
  
  
  METHODS
  We generated apoE and FcRγ double-knockout (FcRγ/apoE-KO) mice, and subsequently introduced several kinds of human recombinant apoE genes. At 21 days after infection, the mice were sacrificed and histologically examined. Peritoneal macrophages were evaluated for their response to modified lipids.
  
  
  RESULTS
  In the FcRγ/apoE-KO mice, the human apoE3-injected mice showed the most drastic LPG-like changes, as well as prominent hypertriglyceridemia. Meanwhile, relative to the human apoE3-injected mice, the FcRγ/apoE-KO mice showed greater lipoprotein deposition and less macrophage infiltration into the mesangial area. Moreover, the peritoneal macrophages in the apoE/FcRγ-KO mice were impaired in lipid uptake and secretion of the cytokines monocyte chemotactic protein-1 and regulated upon activation, normal T-cell expressed and secreted, after the uptake of oxidized low-density lipoprotein.
  
  
  CONCLUSIONS
  These results suggest that the impairment of macrophage function resulting from FcRγ deficiency plays a principal role in the development of LPG in the presence of apoE abnormalities.
authors.affiliation: Department of Internal Medicine, Fukuoka University School of Medicine,Fukuoka, Japan. kito@adm.fukuoka-u.ac.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Ito
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Maho
authors.initials: M
authors.lastname: Watanabe
authors.forename: Atsunori
authors.initials: A
authors.lastname: Ishimura
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Miyahara
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Tetsuhiko
authors.initials: T
authors.lastname: Yasuno
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ifuku
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Sasatomi
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
mesh_terms: D000818:Animals; D053318:Apolipoprotein E3 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017452:Receptors, IgG / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism
chemical_list: D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D008055:Lipids; D008077:Lipoproteins, LDL; D017452:Receptors, IgG; D011994:Recombinant Proteins; C099252:oxidized low density lipoprotein