BCL-2 EXPRESSION AND APOPTOSIS IN NEPHROTOXIC NEPHRITIS

The product of the Bcl-2 proto-oncogene has been shown to prolong cell survival by preventing apoptosis in several cell lineages. To investi gate the regulatory mechanisms of apoptosis in glomerulonephritis, we examined the expression pattern of the Bcl-2 protein together with cel lular events in rat nephrotoxic nephritis. Bcl-2 protein and prolifera ting cell nuclear antigen were detected in glomeruli by immunohistoche mistry. Morphologic changes of apoptosis were identified by electron a nd light microscopy and an in situ DNA nick end labeling method. The f irst (heterologous) phase began with significant neutrophil infiltrati on shortly after the injection of nephrotoxic serum. Both Bcl-2 expres sion and the number of proliferating cells in the glomeruli were at ma ximum at 24 h in the heterologous phase. Glomerular hypercellularity w ith an influx of macrophages and the number of apoptotic glomerular ce lls peaked on day 14 in the second (autologous) phase. Glomerulonephri tis resolved after that. These results suggest that overexpression of the Bcl-2 protein may play a role in glomerular cell survival and exac erbation of glomerulonephritis. Apoptosis may occur as an active mecha nism in the resolution of the autologous phase in nephrotoxic nephriti s.