Endogenous α 2-antiplasmin does not enhance glomerular fibrin deposition or injury in glomerulonephritis

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 tubulointer-stitium. 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 tubuloin-terstitium and in segmentai deposits within some glomeruli. α2-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 fibrino-lytic 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 fibrindeposition, crescent formation or renal impairment in crescentic GN.