Bou-Gharios G, Abraham D, Olsen I
Cell Enzymology Unit, Kennedy Institute of Rheumatology, Hammersmith, London, UK.
Histochem J. 1993 Sep;25(9):593-605. doi: 10.1007/BF00157873.
Lysosomal diseases result from deficiency of one of the many enzymes involved in the normal, step-wise breakdown of macromolecules. Studies in vitro have shown that cells from enzyme-deficient patients can be corrected by an exogenous supply of the missing enzyme. This occurs by receptor-mediated endocytosis of normal enzyme added to tissue culture medium and also by direct transfer from normal leukocytes during cell-to-cell contact. Immunohistochemical analysis has revealed that these processes have similar pathways of intracellular transport of the acquired enzymes, which ultimately reach mature lysosomes in the recipient cells. Moreover, recent studies suggest that both mechanisms are important in the therapy of lysosomal storage diseases by bone marrow transplantation. Advances in gene technology are likely to improve the successful treatment of these disorders, by facilitating the large scale production of clinically effective proteins and also by enabling the stable and safe introduction of normal lysosomal genes into cells of affected patients.
溶酶体疾病是由于参与大分子正常逐步分解的多种酶中的一种缺乏所致。体外研究表明，通过外源性供应缺失的酶，可以纠正酶缺乏患者的细胞。这通过受体介导的内吞作用实现，即添加到组织培养基中的正常酶被内吞，也通过细胞间接触时正常白细胞的直接转移实现。免疫组织化学分析表明，这些过程在获得的酶的细胞内运输方面具有相似的途径，这些酶最终到达受体细胞中的成熟溶酶体。此外，最近的研究表明，这两种机制在骨髓移植治疗溶酶体贮积病中都很重要。基因技术的进步可能会改善这些疾病的成功治疗，这是通过促进临床有效蛋白质的大规模生产，以及通过使正常溶酶体基因稳定、安全地导入受影响患者的细胞来实现的。
