HYPERACTIVITY OF CATHEPSIN-B AND OTHER LYSOSOMAL-ENZYMES IN FIBROBLASTS EXPOSED TO AZITHROMYCIN, A DICATIONIC MACROLIDE ANTIBIOTIC WITH EXCEPTIONAL TISSUE ACCUMULATION

Azithromycin accumulates in lysosomes where it causes phospholipidosis . In homogenates prepared by sonication of fibroblasts incubated for 3 days with azithromycin (66 mu M), the activities of sulfatase A, phos pholipase A(1), N-acetyl-beta-hexosaminidase and cathepsin B increased from 180 to 330%, but not those of 3 non-lysosomal enzymes, The level of cathepsin B mRNA was unaffected, The hyperactivity induced by azit hromycin is non-reversible upon drug withdrawal, prevented by coincuba tion with cycloheximide, affects the V-max but not the K-m, and is not reproduced with gentamicin, another drug also causing lysosomal phosp holipidosis. The data therefore suggest that azithromycin increases th e level of lysosomal enzymes by a mechanism distinct from the stimulat ion of gene expression but requiring protein synthesis, and is not in direct relation to the lysosomal phospholipidosis.