title: Increased 5-lipoxygenase activating protein in immune-mediated experimental nephritis.
abstract: BACKGROUND
  The binding of 5-lipoxygenase (5-LO) to 5-LO activating protein (FLAP) is a prerequisite for subsequent formation of leukotrienes from arachidonic acid.
  
  
  METHODS
  We investigated the localization of FLAP in a rat model of accelerated anti-glomerular basement membrane nephritis and protein expression in cultured rat glomerular endothelial cells.
  
  
  RESULTS
  As expected, 5-LO staining was intense and localized exclusively to perinuclear region and inside the nucleus of leukocytes and macrophages. In these cells, FLAP immunoreactivity co-localized with that of 5-LO, and was restricted to nuclear envelope. Surprisingly, intense nuclear and cytoplasmic staining for FLAP was also observed in glomerular endothelial cells in early experimental glomerulonephritis. Although 5-LO and FLAP mRNA were detected in cultured rat glomerular endothelial cells by RT-PCR, Western blot revealed only FLAP and no 5-LO protein. FLAP protein was regulated in glomerular endothelial cells by the proinflammatory cytokine, interferon-gamma, in a dose-dependent manner.
  
  
  CONCLUSIONS
  The unexpected discovery of FLAP in glomerular endothelial cells in this model of glomerulonephritis, coupled with our demonstration that oral FLAP antagonist therapy reduces proteinuria in human glomerulonephritis and animal models of diabetes, provides further impetus to examine the role of this pro-inflammatory protein in glomerular immune injury.
authors.affiliation: Renal Division, Emory University School of Medicine, Atlanta, USA.
authors.forename: Angel
authors.initials: A
authors.lastname: Montero
authors.forename: Susumu
authors.initials: S
authors.lastname: Uda
authors.forename: Uddhav
authors.initials: U
authors.lastname: Kelavkar
authors.forename: Ashio
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Kamal F
authors.initials: KF
authors.lastname: Badr
authors.forename: Karen A
authors.initials: KA
authors.lastname: Munger
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001485:Basement Membrane / Q000276:immunology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004727:Endothelium / Q000201:enzymology; D004789:Enzyme Activation; D005921:Glomerulonephritis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007114:Immunization; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D016253:Microscopy, Immunoelectron; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; C548594:Alox5ap protein, rat; D002352:Carrier Proteins; D018836:Inflammation Mediators; D008565:Membrane Proteins; D007371:Interferon-gamma; D001094:Arachidonate 5-Lipoxygenase