Abstract 1995 Poster Session II, Sunday, 5/2 (poster 196)

We have previously reported the development of an extensive tubulointerstitial injury in a model of glomerulonephritis produced in C57/B6 mice with a 6 week course of intraperitoneal horse spleen apoferritin (HSA) and lipopolysaccharide (LPS). Interstitial injury is preceded by the appearance of tubular mRNA for C3; we have hypothesized that local synthesis and activation of complement is critical to this process.

To define further the mechanism of this tubulointerstitial damage, we took kidney sections from animals treated with HSA and LPS for 0 to 6 weeks; animals receiving saline injection served as controls. Sections were analyzed for DNA strand breaks using TdT mediated dUTP nick end labeling. RNA was also isolated from kidneys.

Positive tubulointerstitial cells were counted and expressed per mm2. From a baseline of 2.7 at time 0, apoptotic cells increased to 23.5 and 40.9 at 4 and 6 weeks respectively. These times corresponded to those of maximal C3 gene expression by in situ hybridization. At 6 weeks, there was also evidence of down regulation of the apoptosis inhibitor genes DAD-1, Bcl-W and Bcl-xL.

These findings are consistent with a role for apoptosis in the tubulointerstitial component of this model of chronic glomerulonephritis, and a role for local complement synthesis and activation in the initiation of apoptosis.