The effect of lysosomal storage diseases on secretory cells: an ultrastructural study of pancreas as an example.

The lysosome is the disposal and recycling center of eukaryotic cells. The pancreas is an exocrine and endocrine organ. It contains different cell types secreting enzymes, hormones, ions and fluid. The purpose of this study was to demonstrate that the manifestation of the disease in individual cells depends on the expression of the defected gene within the function of the cells. We have thus compared the ultrastructural features of normal pancreas to pancreas affected by eleven different lysosomal storage diseases in human, cats, dogs and mice. The diseases studied include GM1- and GM2- gangliosidosis, galactosialidosis, alpha-mannosidosis, mucopolysaccharidosis-I (MPS-I), mucopolysaccharidosis-VI (MPS-VI), mucopolysaccharidosis-VII (MPS-VII), mucolipidosis-IV (ML-IV), Niemann-Pick C, neuronal ceroid-lipofuscinosis, and an undefined glycolipid storage disease. We demonstrated that morphological changes are seen in some pancreatic cell types but not in others, even though the genetic defect occurs in all cell types. Furthermore, we identified and characterized primary and secondary changes in affected cells. The primary changes include presence of numerous and/or enlarged secondary lysosomes laden with partially degraded substrates. The secondary changes were associated with an abnormal formation and maturation of zymogen or secretory granules. The mechanisms contributing to the secondary changes are thought to be associated with altered synthesis of various constituents of these granules.