CHEDIAK-HIGASHI LYMPHOBLASTOID CELL-LINES - GRANULE CHARACTERISTICS AND EXPRESSION OF LYSOSOME-ASSOCIATED MEMBRANE-PROTEINS

Chediak-Higashi syndrome (CHS) is characterized morphologically by the presence of giant lysosomal granules resulting from the dysregulated fusion of primary lysosomes. Lysosome-associated membrane proteins comprise a family of highly glycosylated proteins which are postulated to facilitate many aspects of normal lysosomal function. In this study, Epstein-Barr virus-transformed lymphoblastoid cell lines derived from a patient with CHS were analyzed for the presence of giant granules and the expression of the lysosome-associated membrane proteins lamp1 and lamp2. Giant myeloperoxidase positive granules typical of CHS, which had a complex structure when examined by electron microscopy, could be demonstrated in the lymphoblastoid cell lines. In situ immunofluorescence with antibodies directed against lamp1 and lamp2 demonstrated abundant expression of each of these proteins in the giant CHS granules. Lack of expression of lysosomal cathepsin G in these granules was also noted. These observations suggest that the lymphoblastoid cell lines provide a convenient model for the study of Chediak-Higashi granules and the lysosome-associated membrane proteins and provide additional evidence that CHS is a "lysosomal" disease. Further study will be necessary to delineate whether the function of these membrane proteins is altered in Chediak-Higashi syndrome. © 1992.