Defective function of renal lysosomes in mice with the Chediak-Higashi syndrome.

Morphologically abnormal lysosomes demonstrated in individuals with the Chediak-Higashi syndrome (CHS) suggested a defect in the function of these abnormal lysosomes. To gain direct experimental evidence of such a defect, horseradish peroxidase (HRP) was injected intravenously into CHS and control mice, the mice killed at varying intervals and the kidneys studied by ultrastructural cytochemistry. No morophologic difference was observed in the absorption and uptake of HRP by proximal convoluted tubules in the two groups of mice. In CHS mice, however, some of the HRP fused with enlarged lysosomes. By 48 hours after injection, the lysosomes of normal mice had digested all but trace amounts of HRP, whereas large amounts were still present in CHS mice at this time. In CHS mice, moderate amounts were still present at 72 hours and trace amounts 96 hours post injection. This slowed rate of digestion of HRP by lysosomes of the proximal convoluted tubule cells of CHS mice suggests a similar defect in all cells in CHS individuals in which there is a lysosomal degradation of protein or other matter obtained by endocytosis. Such a defect may explain some manifestations of impaired host defense observed in CHS.