Aflaki Elma, Borger Daniel K, Grey Richard J, Kirby Martha, Anderson Stacie, Lopez Grisel, Sidransky Ellen
Section of Molecular Neurogenetics, Medical Genetics Branch, National Institutes of Health, Bethesda, MD, USA.
Flow Cytometry Core, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Haematologica. 2017 Apr;102(4):656-665. doi: 10.3324/haematol.2016.155093. Epub 2016 Dec 23.
Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, is characterized by the presence of glucosylceramide-laden macrophages resulting from impaired digestion of aged erythrocytes or apoptotic leukocytes. Studies of macrophages from patients with type 1 Gaucher disease with genotypes N370S/N370S, N370S/L444P or N370S/c.84dupG revealed that Gaucher macrophages have impaired efferocytosis resulting from reduced levels of p67 and Rab7. The decreased Rab7 expression leads to impaired fusion of phagosomes with lysosomes. Moreover, there is defective translocation of p67 to phagosomes, resulting in reduced intracellular production of reactive oxygen species. These factors contribute to defective deposition and clearance of apoptotic cells in phagolysosomes, which may have an impact on the inflammatory response and contribute to the organomegaly and inflammation seen in patients with Gaucher disease.
戈谢病是一种溶酶体葡萄糖脑苷脂酶遗传性缺乏症，其特征是由于衰老红细胞或凋亡白细胞消化受损而出现富含葡萄糖神经酰胺的巨噬细胞。对1型戈谢病基因型为N370S/N370S、N370S/L444P或N370S/c.84dupG患者的巨噬细胞研究表明，戈谢巨噬细胞的胞葬作用受损，这是由于p67和Rab7水平降低所致。Rab7表达降低导致吞噬体与溶酶体融合受损。此外，p67向吞噬体的转运存在缺陷，导致细胞内活性氧产生减少。这些因素导致吞噬溶酶体中凋亡细胞的沉积和清除存在缺陷，这可能会影响炎症反应，并导致戈谢病患者出现器官肿大和炎症。
