Endogenous alpha2-antiplasmin does not enhance glomerular fibrin deposition or injury in glomerulonephritis.
J Thromb Haemost
; 1(9): 1992-9, 2003 Sep.
Article
de En
| MEDLINE
| ID: mdl-12941042
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.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Fibrine
/
Alpha-2-Antiplasmine
/
Glomérulonéphrite
/
Glomérule rénal
Type d'étude:
Etiology_studies
Limites:
Animals
Langue:
En
Journal:
J Thromb Haemost
Sujet du journal:
HEMATOLOGIA
Année:
2003
Type de document:
Article
Pays d'affiliation:
Australie