Proteolytic enzyme treatment reduces glomerular immune deposits and
proteinuria in passive Heymann nephritis
Nakazawa M., Emancipator S.N., Lamm M.E.
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44 106
J. Exp. Med. 1986, Vol. 164, pp. 1973-1987
388 KA (5-14-2)
Summary
We investigated the effect of proteolytic enzyme treatment on the course
of passive Heymann nephritis (PHN). PHN was induced by intravenous injection
of Heymann antibody into Sprague Dawley rats. Protease-treated rats
received intraperitoneal chymopapain and subtilisin. In rats given subnephritogenic
doses of Heymann antibody (5 or 10 mg, insufficient to cause proteinuria),
glomerular immune deposits were assessed by immunofluorescence and electron
microscopy.
In rats given 5 mg Heymann antibody and treated with protease in the
heterologous phase of the disease (days 1-7), fewer animals were positive
for rabbit IgG and rat IgG, as determined by immunofluorescence on day
12, compared with controls (p <0.01). Rats given 10 mg Heymann antibody
and treated on days 15 were less frequently positive for rabbit IgG
on day 5 than controls (p <0.05). When treatment was given on days
6-12 (autologous phase), fewer rats had glomerular rabbit and rat IgG
compared with controls (p <0.025). Protease treatment of rats given
nephritogenic doses of Heymann antibody (>40 mg, causing proteinuria)
did not result in significant differences in immunofluorescence deposits.
However, protease treatment significantly reduced the number of electron
dense deposits at all doses of antibody (p <0.01). Furthermore, rats
given 60 mg Heymann antibody followed by enzyme treatment in the heterologous
phase (days 1-7) or throughout the autologous phase (days 6-18) had
significantly reduced protein excretion during the autologous phase
compared with control rats (p <0.05). After onset of significant
proteinuria on day 15 in rats given 40 mg Heymann antibody and treated
from day 15 until day 25, there was significantly less (p <0.05)
proteinuria on days 21-22 and 24-25 than in control rats; thus, enzymes
could reverse proteinuria. In normal rats, administration of proteases
did not have significant effects on urinary protein excretion, serum
creatinine, or renal morphology, nor did protease affect anti-rabbit
IgG antibody production in rats injected with Heymann antibody. The
overall results indicate that proteolytic enzyme treatment can prevent
or remove glomerular immune deposits and can prevent or reverse proteinuria.
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