Blood group B glycosphingolipids (B-GSLs) are substrates of the lysosomal alpha-galactosidase A (AGAL). Similar to its major substrate-globotriaosylceramide (Gb3Cer)-B-GSLs are not degraded and accumulate in the cells of patients affected by an inherited defect of AGAL activity (Fabry disease-FD).The pancreas is a secretory organ known to have high biosynthesis of blood group GSLs. Herein, we provide a comprehensive overview of the biochemical and structural abnormalities in pancreatic tissue from two male FD patients with blood group B. In both patients, we found major accumulation of a variety of complex B-GSLs carrying predominantly hexa- and hepta-saccharide structures. The subcellular pathology was dominated by deposits containing B-glycoconjugates and autofluorescent ceroid. The contribution of Gb3Cer to the storage was minor. This abnormal storage pattern was specific for the pancreatic acinar epithelial cells. Other pancreatic cell types including those of islets of Langerhans were affected much less or not at all.Altogether, we provide evidence for a key role of B-antigens in the biochemical and morphological pathology of the exocrine pancreas in FD patients with blood group B. We believe that our findings will trigger further studies aimed at assessing the potential pancreatic dysfunction in this disease.
- MeSH
- ABO systém krevních skupin metabolismus MeSH
- acinární buňky metabolismus ultrastruktura MeSH
- beta-buňky metabolismus ultrastruktura MeSH
- Fabryho nemoc krev metabolismus patologie MeSH
- galaktosa analýza metabolismus MeSH
- glykosfingolipidy chemie metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- pankreas metabolismus ultrastruktura MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
181 s. ; 21 cm
Dopl. vyd. 222 s. : il., tab. ; 22 cm
- MeSH
- ABO systém krevních skupin metabolismus MeSH
- dietetika MeSH
- jídelníček MeSH
- vaření MeSH
- Publikační typ
- kuchařské knihy MeSH
- příručky MeSH
Galectin-3 is an immunomodulatory protein with binding capacity for various glycoconjugates including IgE. It has been shown to be produced by epidermal keratinocytes and is present on the surfaces of skin Langerhans cells (LC). Therefore, it may have a role in the pathogenesis of various skin diseases, such as atopic dermatitis. To study the expression of galectin-3 in LC, we used, in addition to specific antibodies, a panel of synthetic, carrier-immobilized, specific oligosaccharides of the A- and B-histo-blood group, which are recognized by this lectin. In the mean time, Birbeck granules were visualized with an anti-Lag antibody. The double labeling experiments showed a remarkable colocalization of signals for Lag antigen (Birbeck granules) and galectin-3, as well as the binding sites for A- and B-histo-blood group trisaccharides. The specificity of the oligosaccharide binding was demonstrated by the lack of binding by Le(c), Le(d) (H blood group antigen), and sLe(x), which are not recognized by galectin-3. These results suggest that galectin-3 is present in Birbeck granules, where it retains reactivity for its glycoligands.
- MeSH
- ABO systém krevních skupin * metabolismus MeSH
- cytoplazmatická granula imunologie MeSH
- diferenciační antigeny genetika metabolismus MeSH
- galektin 3 MeSH
- Langerhansovy buňky imunologie metabolismus MeSH
- lidé MeSH
- protilátky imunologie MeSH
- trisacharidy * metabolismus MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
