Structural changes in lysosomes from cultured human fibroblasts in Duchenne's muscular dystrophy.

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Abstract
A decreased activity of the lysosomal enzyme dipeptidyl aminopeptidase-I (DAP-I) was reported in cultured fibroblasts from patients with Duchenne muscular dystrophy (DMD). EM examination of these cells reveals the presence of abundant lamellar bodies, a morphologic abnormality commonly associated with impaired lysosomal function. Morphometric analysis of these cytoplasmic figures in dystrophic cells shows a 7-fold increase relative to normal controls (P < 0.01). Analysis of lysosomal density profiles by density gradient centrifugation reveals similar patterns in normal and DMD cells. Treatment of lysosomes with the nonionic detergent Triton X-100 causes activation of DAP-I. This activation, attributable to structure-linked latency, is markedly diminished in DMD cells which show an optimal activation of 180% compared to 255% for control fibroblasts (P < 0.01). An alteration in the properties of the lysosomal membrane in DMD fibroblasts was suggested. Studies on the release of DAP-I from lysosomes by osmotic shock showed it to be a membrane-associated enzyme with membrane-binding characteristics intermediate between those of tightly bound .beta.-glucosidase and those of unbound N-acetylgalactosaminidase. The latency characteristics of these other lysosomal enzymes are not altered in the DMD cells, indicating that the effect is specific for DAP-I.