The temporal relationship between glomerular cell proliferation and monocyte infiltration in experimental glomerulonephritis.

Abstract

During the course of an accelerated form of anti-glomerular basement membrane nephritis in rats, the authors determined the temporal relationships between (a) glomerular hypercellularity, (b) kinetics of cell proliferation and (c) monocyte infiltration in glomeruli. Although glomerular hypercellularity was not appreciable or mild by qualitative histology, mean glomerular cell counts rose between days two and six of nephritis by up to 30% over controls. Cell proliferation in glomeruli was assessed 2 h after pulse label with3H-thymidine by determining histoautoradiographic cell labeling indices (LI) and by measuring the total radioactivity of isolated glomeruli (TGA). On day one, mean LI of cells in Bowman’s capsule was increased by 356% over controls and fell subsequently. LI values of tuft cells rose more gradually, reaching a maximum increment of 405% on day four. TGA also increased on day one and two, and peaked on day four. In additional rats, studied in parallel,3H-thymidine incorporation was measured 48 h after the pulse in order to allow time for the labeling and glomerular influx of monocytes derived from dividing extra-renal precursors. In rats sacrificed on the first day of nephritis, the prolonged labeling time did not result in further gains of tuft LI or of TGA over values obtained 2 h after the pulse. On day four, by contrast, the 48-h labeling time was associated with markedly higher results for LI and TGA than the 2-h interval. These findings indicated that the glomerular influx of labeled blood-borne monocytes was not appreciable on day one but increased markedly between day two and day four. This was supported by histochemical studies for non-specific esterase which revealed a similar time course for the presence of monocytes in glomeruli by showing few esterase-positive monocytes in the early stage and many after day two. The results demonstrate that this model of glomerulonephritis is characterized by markedly enhanced replication of intrinsic glomerular cells, beginning on the first day of the injury at a time when the glomerular influx of monocytes is inconspicuous. Increases of glomerular cell prolifertion become most pronounced over the following days when they are associated with a sizeable monocytic infiltrate. The prominent cellular response in glomeruli is revealed by the applied quantitative methods in the absence of histologically impressive glomerular hypercellularity.