Fibroblasts acquire beta-glucuronidase by direct and indirect transfer during co-culture with macrophages.
Macrophages can transfer beta-glucuronidase directly to co-cultured fibroblasts during cell-to-cell contact as well as indirectly via receptor-mediated endocytosis. The degree of enzyme activity acquired by the deficient fibroblasts was determined by the ratio of donor to recipient cells and by the length of time for which cells were allowed to interact. Both mechanisms of transfer were efficient so that 70% of normal enzyme activity was restored to deficient fibroblasts after 24 h of co-culture. These observations show that macrophages have great potential as donor cells in replacement therapy for the treatment of inherited lysosomal enzyme deficiency diseases.
D000818:Animals; D002450:Cell Communication; D002478:Cells, Cultured; D004705:Endocytosis; D005347:Fibroblasts / Q000201:enzymology* / Q000502:physiology; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000502:physiology; D008264:Macrophages / Q000201:enzymology* / Q000502:physiology; D008360:Mannosephosphates / Q000494:pharmacology; D051379:Mice; D008808:Mice, Inbred CBA
D008360:Mannosephosphates; C027693:mannose-6-phosphate; D005966:Glucuronidase