Defective lysosomal enzyme secretion in kidneys of Chediak-Higashi (beige) mice.

Abstract

The beige mouse is an animal model for the human Chediak-Higashi syndrome, a disease characterized by giant lysosomes in most cell types. In mice, treatment with androgenic hormones causes a 20-50-fold elevation in at least one kidney lysosomal enzyme, ~-glucuronidase. Beige mice treated with androgen had significantly higher kidney ~-glucuronidase, B-galactosidase, and N-acetyl-~-oglucosaminidase (hexosaminidase) levels than normal mice. Other androgeninducible enzymes and enzyme markers for the cytosol, mitochondria, and peroxisomes were not increased in kidney of beige mice. No significant lysosomal enzyme elevation was observed in five other organs of beige mice with or without androgen treatment, nor in kidneys of beige females not treated with androgen.Histochemical staining for glucuronidase together with subcellular fractionation showed that the higher glucuronidase content of beige mouse kidney is caused by a striking accumulation of giant glucuronidase-containing iysosomes in tubule cells near the corticomedullary boundary. In normal mice lysosomal enzymes are coordinately released into the lumen of the kidney tubules and appreciable amounts of lysosomal enzymes are present in the urine. Levels of urinary lysosomal enzymes are much lower in beige mice than in normal mice.

Giant granules of neutrophils in Chediak-Higashi syndrome are derived from azurophil granules but not from specific and gelatinase granules

“…We found a more pronounced reduction in mobilization of myeloperoxidase than previously published by others [10,11]. The deficient giant granule mobilization is not restricted to neutrophils but has also been demonstrated in other cell types, including tubular kidney cells, cytotoxic T lymphocytes, and natural killer cells [27,28].…”

HIV-1 Nef Promotes Endocytosis of Cell Surface MHC Class II Molecules via a Constitutive Pathway

“…However, MHCII molecules may recycle through an early endosomal compartment dependent on the homologous fusion of early endosomes controlled by Rab5 so that the lack of Rab5 activity may lead to default delivery to late endosomes and then by normal endolysosomal Rab7-dependent maturation mechanisms to the lysosomes. Because Bg cells show defective trafficking to the late endosomal compartments and increased ability of these lysosomes to fuse with the plasma membrane (42,43), the loss of Nef-mediated MHCII down-regulation in Bg cells can perhaps be explained either by enhanced recycling back to the cell surface from early endosomes and/or by fusion of Bg lysosomes with the plasma membrane.…”

Defective release of α granule and lysosome contents from platelets in mouse Hermansky-Pudlak syndrome models

“…Lysosomal enzyme activity in whole-cell lysates and releasates was measured for b-hexosaminidase by a colorimetric assay using P-nitrophenyl-N-acetyla-D-glucosaminide as a substrate, 49 and was measured for b-glucuronidase using the fluorogenic substrate 4-methylumbelliferyl-b-D-glucuronide (EMD Millipore, Billerica, MA). 50 Laser-induced thrombus formation in mouse cremaster muscle arterioles…”