ORIGIN OF GLOMERULAR CRESCENTS IN EXPERIMENTAL NEPHROTOXIC SERUM NEPHRITIS IN RABBIT

Abstract

The origin of glomerular crescents and diffuse hypercellularity was investigated in rabbits receiving a single i.v. injection of nephrotoxic serum. Experiments to demonstrate local glomerular proliferation included mitotic counting at intervals after nephrotoxic serum and autoradiography of kidneys 1 h after pulse 3H-thymidine labeling. There was an increase in local endocapillary proliferation between days 4 and 6 when severe diffuse hypercellularity developed. From days 8-13 during crescent formation there was considerable local epithelial proliferation. To assess the role of infiltrating bone marrow cells a new technique of renal transplantation in rabbits was developed. Kidneys from unlabeled donors were transplanted on day 4 or day 9 into recipients prelabeled with 3H-thymidine, and labeled cells were sought in glomeruli of transplants 1-4 days later. Large numbers of labeled cells appeared on days 5-6 in areas of endocapillary hypercellularity in glomeruli of animals given transplants on day 4 indicating a significant influx of bone marrow cells. In kidneys transplanted on day 9, few labeled cells were present in crescents on days 10-11. Autoradiographic labeling of mononuclear phagocytes in carrageenan granulomas and interstitial renal infiltrates in recipients were used as positive controls of bone marrow cell labeling. In the early phase of diffuse hypercellularity there is considerable blood monocyte infiltration, whereas crescents which develop later are principally the result of glomerular epithelial cell proliferation.