Expression of the lysosome-associated membrane proteins in myopathies with rimmed vacuoles

Abstract.

Lysosome-associated membrane proteins (LAMPs) are structural glycoproteins located on the lysosomal membrane and are thought to have an important role in protein degradation. Increased lysosomal activity is associated with the formation of rimmed vacuoles, which are observed in various muscle disorders such as inclusion body myositis (IBM) and distal myopathy with rimmed vacuole (DMRV). In the present study, we examined LAMP-1 and LAMP-2 in biopsied muscle specimens from four cases of sporadic IBM and two of DMRV, as well as six of myopathies without rimmed vacuoles. In all cases of IBM and DMRV, immunohistochemistry showed accumulation of LAMPs in the rimmed vacuoles and the subsarcolemmal portion of the vacuolated fibers. Immunoreactivities of LAMPs in the vacuolated fibers were often associated with those of cathepsin D; however, cathepsin D was not expressed on some LAMP-positive fibers. Further, atrophic muscle fibers were sometimes positive for LAMPs expression. These findings were more prominent in LAMP-2 than in LAMP-1. Thus, LAMP-2 may play an important role in the increased protein degradation in diseased muscle fibers. The increased expression of LAMPs in the vacuolated muscle fibers may be associated with the formation of rimmed vacuoles in IBM and DMRV.