Fate of exogenous peroxidase in renal lysosomes of mice with Chediak-Higashi syndrome.

The beige mouse is a homolog of Chediak-Higashi syndrome, a disorder which is characterized by the presence of enlarged (anomalous) lysosomes in many cell types. In kidney, anomalous lysosomes are present in cells of the proximal convoluted tubules. In this study, the degradation of injected horseradish peroxidase (HRP) in lysosomes was studied in both the convoluted (S1-S2) and straight (S3) segments of the proximal tubules of beige and control (C57 B1) mice. Tissues were removed at intervals from 18 hours to 7 days after HRP injection. Peroxidase activity was visualized for light and electron microscopy by incubating sections in diaminobenzidine medium. No differences in the rate of degradation of HRP were demonstrable between anomalous lysosomes in S1-S2 cells of beige kidney and those in controls. In both animals, HRP was demonstrable in these lysosomes at 18 and 36 hours but not at 48 hours after injection. By electron microscopy, reaction product appeared as a flocculent precipitate distributed uniformly throughout the lysosome. In contrast to those of S1-S2 cells, lysosomes of beige S3 cells degraded HRP much more slowly than did those of control mice. In controls, HRP was demonstrable in S3 lysosomes at 18 hours but not at 48 hours after injection. In beige mouse kidney HRP was demonstrable in many S3 lysosomes at 48 hours, and it persisted in some lysosomes as long as 5 days after injection. These findings indicate that beige S3 lysosomes are defective in degrading protein. As reported recently, these lysosomes are also markedly enlarged and altered in content. They appear to arise as part of a renal lesion of unknown pathogenesis which is confined to the S3 segments of the proximal tubules. The slower rate of degradation of protein appears to be another manifestation of the alteration in these lysosomes.