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Endogenous α 2 ‐antiplasmin does not enhance glomerular fibrin deposition or injury in glomerulonephritis
Author(s) -
Kitching A. R.,
Turner A. L.,
O'Sullivan KM.,
Dewerchin M.,
Lijnen H. R.
Publication year - 2003
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1046/j.1538-7836.2003.00389.x
Subject(s) - fibrin , plasmin , plasminogen activator , fibrinolysis , glomerulonephritis , medicine , renal function , endocrinology , chemistry , kidney , tissue plasminogen activator , creatinine , glomerular basement membrane , urokinase , immunology , biochemistry , enzyme
Summary. 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. α 2 ‐Antiplasmin (α 2 ‐AP) is the major circulating inhibitor of plasmin and is expressed in the renal tubulointerstitium. Objective : To determine whether endogenous α 2 ‐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 α 2 ‐AP (α 2 ‐AP +/+ and α 2 ‐AP −/− mice). Results : In mice with crescentic GN, α 2 ‐AP was detected in the tubulointerstitium and in segmental deposits within some glomeruli. α 2 ‐AP +/+ mice developed crescentic GN (38 ± 9% glomeruli affected) with glomerular fibrin deposition and renal impairment (serum creatinine 30 ± 1 µmol L −1 , normal without GN 11 ± 1 µmol L −1 ). Genetic deficiency of α 2 ‐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 µmol L −1 ). α 2 ‐AP was unmeasurable in kidneys from α 2 ‐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. α 2 ‐AP −/− mice did have enhanced total renal fibrinolytic capacity as assessed by in situ fibrin overlay (α 2 ‐AP +/+ 0.19 ± 0.01, α 2 ‐AP −/− 0.36 ± 0.03 lyzed area/total area). Conclusions : α 2 ‐AP is not important to net glomerular fibrin deposition, crescent formation or renal impairment in crescentic GN.