Ar. Kitching et al., PLASMINOGEN AND PLASMINOGEN ACTIVATORS PROTECT AGAINST RENAL INJURY IN CRESCENTIC GLOMERULONEPHRITIS, The Journal of experimental medicine, 185(5), 1997, pp. 963-968
The plasminogen/plasmin system has the potential to affect the outcome
of inflammatory diseases by regulating accumulation of fibrin and oth
er matrix proteins. In human and experimental crescentic glomeruloneph
ritis (GN), fibrin is an important mediator of glomerular injury and r
enal impairment. Glomerular deposition of matrix proteins is a feature
of progressive disease. To study the role of plasminogen and plasmino
gen activators in the development of inflammatory glomerular injury, G
N was induced in mice in which the genes for these proteins had been d
isrupted by homologous recombination. Deficiency of plasminogen or com
bined deficiency of tissue type plasminogen activator (tPA) and urokin
ase type plasminogen activator (uPA) was associated with severe functi
onal and histological exacerbation of glomerular injury. Deficiency of
tPA, the predominant plasminogen activator expressed in glomeruli, al
so exacerbated disease. uPA deficiency reduced glomerular macrophage i
nfiltration and did not significantly exacerbate disease. uPA receptor
deficiency did not effect the expression of GN. These studies demonst
rate that plasminogen plays an important role in protecting the glomer
ulus from acute inflammatory injury and that tPA is the major protecti
ve plasminogen activator.