title: Efficacy of galectins in the amelioration of nephrotoxic serum nephritis in Wistar Kyoto rats.
abstract: BACKGROUND
  Galectins are characterized by specific affinity for beta-galactoside sugars, and they play a role in diverse biological processes, including cell adhesion, cell proliferation, and apoptosis. Galectin-1, -3, and -9 have been implicated in modulating the immune response.
  
  
  METHODS
  Nephrotoxic serum nephritis, which is characterized by crescent formation and glomerular influx of CD8+ cells into glomerular capillaries, was induced in Wistar Kyoto (WKY) rats by injecting rabbit antiglomerular basement membrane serum. Following induction, the rats were treated either with phosphate-buffered saline or dexamethasone, galectin-1, galectin-3, or galectin-9 on alternate days and were sacrificed at day 14. At day 8, splenic lymphocytes were isolated and employed for terminal deoxytransferase-mediated uridine triphosphate nick end-labeling (TUNEL) assay to assess the degree of apoptosis, and the kidneys were utilized to determine the extent of influx of CD4(+) and CD8(+) cells and glomerular damage.
  
  
  RESULTS
  Dexamethasone induced a marked apoptosis of splenic CD4(+) and CD8(+) cells, and it inhibited the production of anti-rabbit IgG and the influx of CD8+ cells and macrophages into the renal glomeruli. Crescent formation and excretion of urinary proteins were also reduced. Galectin-9 failed to induce apoptosis in the CD4(+) cells; however, it induced apoptosis in the CD8(+) cells and inhibited the infiltration of CD8(+) cells. Although galectin-1 and -3 did not induce the apoptosis in the T cells, they inhibited the accumulation of macrophages in the renal glomeruli. Like dexamethasone, the galectins also reduced the crescentic formation, proliferation of glomerular cells, and excretion of urinary proteins.
  
  
  CONCLUSIONS
  Galectin-9 selectively induces apoptosis of the activated CD8(+) cells, while the macrophage influx into the kidney is modulated by all three galectins. This finding raises an interesting possibility for the utility of galectins in the modulation of macrophages that are involved in immune-mediated glomerular diseases.
authors.affiliation: Department of Medicine III, Okayama University Medical School, Okayama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tsuchiyama
authors.forename: J
authors.initials: J
authors.lastname: Wada
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.forename: K
authors.initials: K
authors.lastname: Hiragushi
authors.forename: K
authors.initials: K
authors.lastname: Hida
authors.forename: K
authors.initials: K
authors.lastname: Shikata
authors.forename: M
authors.initials: M
authors.lastname: Yamamura
authors.forename: Y S
authors.initials: YS
authors.lastname: Kanwar
authors.forename: H
authors.initials: H
authors.lastname: Makino
mesh_terms: D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000943:Antigens, Differentiation / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001323:Autoantibodies; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; D005938:Glucocorticoids / Q000627:therapeutic use; D006388:Hemagglutinins / Q000378:metabolism / Q000627:therapeutic use*; D007106:Immune Sera / Q000276:immunology*; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000473:pathology; D037102:Lectins / Q000378:metabolism / Q000627:therapeutic use*; D009393:Nephritis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology / Q000652:urine; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011921:Rats, Inbred WKY; D013154:Spleen / Q000503:physiopathology; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; D000943:Antigens, Differentiation; D001323:Autoantibodies; D037483:Galectin 1; D037502:Galectin 3; D037161:Galectins; D005938:Glucocorticoids; D006388:Hemagglutinins; D007106:Immune Sera; C105032:LGALS9 protein, human; D037102:Lectins; C051951:antiglomerular basement membrane antibody; D003907:Dexamethasone