Abstract
In-vivo BrdU incorporation and visualization by immunohistochemistry, previously reported in normal mouse kidney, were applied to a mouse model of anti-GBM GN, induced by immunization with rabbit anti-mouse GBM antiserum, to assess the contribution of capsular cell proliferation in the development of crescents. A significant increase (P = 0.003) in the BrdU-labelling index (LI) for capsular cells was observed, as compared to normal mice (5.76 +/- 1.1 vs 0.70% +/- 0.12%). Elevated LI were also observed for tuft and tubular cells but these increases were not statistically significant. It was concluded that, in this model, capsular cell proliferation is a major contributory factor to the formation of cellular crescents. In addition, other pathological features, indicative of glomerular damage, were assessed semi-quantitatively alongside numbers of labelled capsular cells per glomerulus. It was found that podocyte vacuolation is strongly associated with, and may precede, proliferation, suggesting some common causative factor. Fibrin, when present, was confined within the tuft capillary loops and was only weakly associated with either podocyte vacuolation or capsular cell proliferation. It was concluded that this protein does not play a major role in the initiation of pathological damage. Finally, glomerular lesions were found to be randomly distributed. Thus, the idea of intraglomerular signalling, resulting in 'clustering' of damaged glomeruli, is not supported.
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