抄録
Sphingolipid activator protein-1 (SAP-1), which stimulates the hydrolysis of several sphingolipids, including sulfatide, is increased in metachromatic leukodystrophy (MLD) and other lipidoses, but the reason for its increase in some lipidoses remains to be discovered. In a previous study, we found that intralysosomal sulfatide storage induced a compensatory increase in SAP-1 in cultured skin fibroblasts of MLD. In this study, the distribution of SAP-1 in the cerebrum of a normal subject and an MLD patient was examined. In the normal cerebral hemispheres, SAP-1 was found in almost all the cell types, especially in the neurons. Its subcellular localization was confirmed to be lysosomal by an electron microscopic study. In contrast, in the MLD cerebrum, SAP-1-positive cells were found throughout the white matter, especially in the corticomedullary junction. These SAP-1-positive cells in the corticomedullary junction were macrophagocyte-like cells, based on their structural characteristics and Mac-1-positive staining, and they had metachromatic granules, which reflect sulfatide storage in MLD. They were also stained with myelin basic protein (MBP) in spite of diffuse myelin loss in the white matter. The corticomedullary junction, known to be spared from demyelination, was actively infiltrated in the advanced stage by macrophagocyte-like cells, in which accumulation of sulfatide induced an increase in SAP-1 in the lysosomes. These results suggest that SAP-1 plays an important role in regulating intracellular lipid catabolism and help explain its increase in some lipidoses.
