Background: Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of α - galactosi...Background: Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of α - galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL- 3). To date, no direct detection of GL- 3 by immunoelectron microscopy has been reported. Objectives: To examine whether GL- 3 is accumulated exclusively in lysosomes of cutaneous cells using an anti- GL- 3 monoclonal antibody (mAb) and immunoelectron microscopy. Methods: Skin specimens from seven patients with Fabry disease were examined immunohistochemically by light and electronmicroscopy using an anti- GL- 3mAb. Results: By light microscopy, the cytoplasm of vascular endothelial cells, eccrine gland cells, and perineurium was stained with mouse anti- GL- 3 antibody. Electronmicroscopically, positive signals for GL- 3 were limited to dilated lysosomes in the cytoplasm of endothelial cells, pericytes, eccrine gland cells, dermal fibroblasts and perineurium. Conclusions: Our results demonstrate that the cytoplasmic deposit in Fabry disease was GL- 3 and the accumulated GL- 3 was localized essentially to lysosomes.展开更多
文摘Background: Fabry disease is characterized by the systemic accumulation of glycosphingolipids, particularly in the lysosomes of vascular endothelial cells of most organs due to the deficient activity of α - galactosidase A. The major glycolipid accumulated in tissue is globotriaosylceramide (GL- 3). To date, no direct detection of GL- 3 by immunoelectron microscopy has been reported. Objectives: To examine whether GL- 3 is accumulated exclusively in lysosomes of cutaneous cells using an anti- GL- 3 monoclonal antibody (mAb) and immunoelectron microscopy. Methods: Skin specimens from seven patients with Fabry disease were examined immunohistochemically by light and electronmicroscopy using an anti- GL- 3mAb. Results: By light microscopy, the cytoplasm of vascular endothelial cells, eccrine gland cells, and perineurium was stained with mouse anti- GL- 3 antibody. Electronmicroscopically, positive signals for GL- 3 were limited to dilated lysosomes in the cytoplasm of endothelial cells, pericytes, eccrine gland cells, dermal fibroblasts and perineurium. Conclusions: Our results demonstrate that the cytoplasmic deposit in Fabry disease was GL- 3 and the accumulated GL- 3 was localized essentially to lysosomes.
