Hůlková H, Ledvinová J, Asfaw B, Koubek K, Kopriva K, Elleder M
Institute of Inherited Metabolic Disorders, Charles University, First Faculty of Medicine and University Hospital, Ke Karlovu 2 128 08, 128 08, Prague 2, Czech Republic.
Virchows Arch. 2005 Jul;447(1):31-44. doi: 10.1007/s00428-005-1246-y. Epub 2005 May 26.
Immunohistochemical studies of the presence of lactosylceramide (LacCer) in lysosomal storage disorders (LSDs) were done using anti-LacCer monoclonal antibody of the CDw 17 type (clone MG-2). No sign of an association between LacCer and the lysosomal system in normal cells was observed, except for histiocytes active in phagocytosis. A comparative study of a group of LSDs showed a general tendency for LacCer to increase in storage cells in Niemann-Pick disease type C (NPC), and types A and B, GM1 gangliosidosis, acid lipase deficiency, glycogen storage disease type II and mucopolysaccharidoses. LacCer accumulated in storage cells despite normal activity of relevant lysosomal degrading enzymes. The accumulation of LacCer displayed variability within storage cell populations, and was mostly expressed in neurons in NPC. An absence of the increase in LacCer in storage cells above control levels was seen in neuronal ceroid lipofuscinoses (neurons and cardiocytes) and in Fabry disease. Gaucher and Krabbe cells showed significantly lower levels, or even the absence, of LacCer compared with control macrophages. Results of immunohistochemistry were corroborated by semiquantitative lipid thin-layer chromatography (TLC). It is suggested that different associations of LacCer with the lysosomal storage process may reflect differences in glycosphingolipid turnover induced by the storage-compromised lysosomal/endosomal system.
利用CDw 17型抗乳糖基神经酰胺（LacCer）单克隆抗体（克隆MG-2），对溶酶体贮积症（LSDs）中LacCer的存在情况进行了免疫组织化学研究。除了活跃于吞噬作用的组织细胞外，在正常细胞中未观察到LacCer与溶酶体系统之间存在关联的迹象。对一组LSDs的比较研究表明，在C型尼曼-匹克病（NPC）、A型和B型、GM1神经节苷脂病、酸性脂肪酶缺乏症、II型糖原贮积病和黏多糖贮积症中，LacCer在贮积细胞中有普遍增加的趋势。尽管相关溶酶体降解酶活性正常，但LacCer仍在贮积细胞中蓄积。LacCer的蓄积在贮积细胞群体中表现出变异性，且在NPC的神经元中表达最为明显。在神经元蜡样脂褐质沉积症（神经元和心肌细胞）和法布里病中，未观察到贮积细胞中LacCer增加至对照水平以上。与对照巨噬细胞相比，戈谢细胞和克拉伯细胞显示出LacCer水平显著降低，甚至缺失。免疫组织化学结果得到了半定量脂质薄层色谱（TLC）的证实。提示LacCer与溶酶体贮积过程的不同关联可能反映了由贮积受损的溶酶体/内体系统诱导的糖鞘脂周转差异。
