Opzioni
The effect of proteinase inhibitors on glomerular albumin permeability induced in vitro by serum from patients with idiopathic focal segmental glomerulosclerosis.
2004
Periodico
NEPHROLOGY DIALYSIS TRANSPLANTATION
Abstract
Background. The putative circulating factor responsible
for the glomerular permeability alterations induced
in vitro by serum from patients affected by focal
segmental glomerulosclerosis (FSGS) remains unidentified.
Wehave observed that a serine proteinase isolated
from patient serum increases albumin permeability in
isolated glomeruli. The objective of the present study
was to determine the effect of various proteinase inhibitors
on glomerular albumin permeability (Palb) in
isolated glomeruli incubated with FSGS serum.
Methods. The study population consisted of 12 FSGS
patients (eight males; mean age: 21±10 years) previously
shown to have elevated serum albumin permeability
activity. Palb was determined by measuring the
change in glomerular volume induced by applying
oncotic gradients to isolated healthy rat glomeruli
treated with patient serum in comparison to control
serum. Solutions of seven different proteinase inhibitors
(0.5 mg/ml) were added to the incubation media
with the sera (1:1 vol/vol): serine proteinase inhibitors
(PMSF, leupeptin, aprotinin, gabexate mesylate), the
cysteine proteinase inhibitor E-64, the metalloproteinase
inhibitor EDTA and the aspartate proteinase
inhibitor pepstatin. Sera from the same patients were
also tested with the addition to the incubation media of
quinaprilat, an inhibitor of the metalloproteinase
angiotensin-converting enzyme.
Results. Mean Palb of the sera was 0.86±0.11, with the
addition of PMSF 0.41±0.09, leupeptin 0.30±0.17,
aprotinin 0.09±0.14, gabexate mesylate 0.27±0.25,
E-64 0.81±0.09, EDTA 0.68±0.10 or pepstatin
0.76±0.11. The mean Palb of the sera combined with
quinaprilat was reduced to 0.34±0.35. Thus, only the
serine proteinase inhibitors consistently blocked the
increased Palb induced by the FSGS sera.
Conclusions. In the cascade of events that lead to the
initiation of glomerular fibrosis in FSGS, the putative
glomerular permeability factor associated with FSGS
may require a serine proteinase to effect its activity.
Archivio
Diritti
metadata only access