title: Endogenous alpha2-antiplasmin does not enhance glomerular fibrin deposition or injury in glomerulonephritis.
abstract: BACKGROUND
  Fibrin deposition is an important mechanism of glomerular injury in crescentic glomerulonephritis (GN), a severe form of immune renal injury. Both coagulation and fibrinolysis (via the plasminogen-plasmin system) are important in net glomerular fibrin accumulation in GN. alpha2-Antiplasmin (alpha2-AP) is the major circulating inhibitor of plasmin and is expressed in the renal tubulointerstitium.
  
  
  OBJECTIVE
  To determine whether endogenous alpha2-AP contributes to glomerular fibrin accumulation in GN.
  
  
  METHODS
  Crescentic autologous phase antiglomerular basement membrane GN was induced in mice with intact and deficient endogenous alpha2-AP (alpha2-AP+/+ and alpha2-AP-/- mice).
  
  
  RESULTS
  In mice with crescentic GN, alpha2-AP was detected in the tubulointerstitium and in segmental deposits within some glomeruli. alpha2-AP+/+ mice developed crescentic GN (38 +/- 9% glomeruli affected) with glomerular fibrin deposition and renal impairment (serum creatinine 30 +/- 1 micro mol L-1, normal without GN 11 +/- 1 micro mol L-1). Genetic deficiency of alpha2-AP did not result in attenuated glomerular fibrin deposition, crescent formation (39 +/- 8% glomeruli affected), glomerular leukocyte infiltration or renal impairment (serum creatinine 33 +/- 7 micro mol L-1). alpha2-AP was unmeasurable in kidneys from alpha2-AP-/- mice, which did not develop compensatory changes in plasminogen, tissue type plasminogen activator (tPA), urokinase type PA (uPA) or plasminogen activator inhibitor-1 proteins, or changes in tPA or uPA activity. alpha2-AP-/- mice did have enhanced total renal fibrinolytic capacity as assessed by in situ fibrin overlay (alpha2-AP+/+ 0.19 +/- 0.01, alpha2-AP-/- 0.36 +/- 0.03 lyzed area/total area).
  
  
  CONCLUSIONS
  alpha2-AP is not important to net glomerular fibrin deposition, crescent formation or renal impairment in crescentic GN.
authors.affiliation: Center for Inflammatory Diseases, Monash University, Department of Medicine, Monash Medical Center, Clayton, Victoria, Australia. richard.kitching@med.monash.edu.au
authors.forename: A R
authors.initials: AR
authors.lastname: Kitching
authors.forename: A L
authors.initials: AL
authors.lastname: Turner
authors.forename: K-M
authors.initials: KM
authors.lastname: O'Sullivan
authors.forename: M
authors.initials: M
authors.lastname: Dewerchin
authors.forename: H R
authors.initials: HR
authors.lastname: Lijnen
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte; D005337:Fibrin / Q000378:metabolism*; D005342:Fibrinolysis; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007678:Kidney Glomerulus / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D051437:Renal Insufficiency / Q000209:etiology; D000979:alpha-2-Antiplasmin / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D000979:alpha-2-Antiplasmin; D005337:Fibrin