title: Effects of leukocytosis and macrophage activation on anti-Thy 1.1 glomerulonephritis in the rat.
abstract: OBJECTIVE
  In anti-Thy 1.1 proliferative glomerulonephritis (GN), glomerular infiltration of polymorphonuclear leukocytes (PMNs) reaches a peak level after 1 h and that of macrophages does so 24 h after induction. However, the roles of PMNs and macrophages in the pathogenesis of anti-Thy 1.1 GN remain unclear. We examined the effects on this model of leukocytosis induced by granulocyte colony-stimulating factor (G-CSF) and of macrophages stimulated by macrophage colony-stimulating factor (M-CSF).
  
  
  METHODS
  Anti-Thy 1.1 GN was induced in male Wistar rats by intravenous injection of OX-7, a monoclonal antibody to the Thy 1 antigen. G-CSF (10 microg/kg/day), M-CSF (20 microg/kg/day) or vehicle was administered intraperitoneally for 7 days starting 24 h before the injection of OX-7. Histological examination of renal biopsy specimens was performed on Days 1, 5 and 14 after induction.
  
  
  RESULTS
  Circulating and glomerular-infiltrating PMNs (RP-3-positive cells) were increased at Day 5 in G-CSF-treated rats compared with controls receiving vehicle, and glomerular mesangiolysis continued at Day 5. The number of proliferating cells positive for proliferating cell nuclear antigen at Day 5 and matrix scores at Day 14 were smaller in G-CSF-treated rats than in control rats. The mesangiolysis score was significantly higher in the G-CSF group than in the control group at Days 5 and 14, but not at Day 1. ED-1-positive cells were increased in number at Day 5 and matrix accumulation decreased at Day 14 in M-CSF-treated rats compared with controls. Serum creatinine level at Day 14 was lower in the M-CSF group, but not in the G-CSF group, compared with the control group.
  
  
  CONCLUSIONS
  Activated macrophages may inhibit excess matrix accumulation and ameliorate the recovery of renal function, whereas leukocytosis inhibits the repair of mesangial cell injury in this model.
authors.affiliation: Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Sugitani, Toyama, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Futamura
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Izumino
authors.forename: Hidenori
authors.initials: H
authors.lastname: Sugawara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
authors.forename: Masanobu
authors.initials: M
authors.lastname: Takata
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005921:Glomerulonephritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000502:physiology; D007964:Leukocytosis / Q000503:physiopathology*; D008262:Macrophage Activation / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018800:Thy-1 Antigens; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor