Abstract
Summary: Mature macrophages obtained by the growth and differentiation of blood monocytes have been used to develop an in vitro system for the study of hereditary human lysosomal storage diseases. Maturation of monocytes into macrophages is rapid, and the maximal activities of the lysosomal hydrolases, β-galactosidase, β-glucuronidase, α-mannosidase, and β-N-acctyl glucosaminidase, is reached by the seventh day in culture. The rate of 35SO4 incorporation into mucopolysaccharides is also maximal at 7 days. Normal macrophages attain a steady state of 35SO4 labeling within 5 hr of culture and degrade about 60% of sulfated mucopolysaccharides in 5 hr. By contrast, macrophages from patients with the Hunter syndrome (MPS II), when grown in MPS II serum, degrade only 19% of sulfated MPS within 12 hr and incorporate more 35SO4 into MPS. Significant correction of the metabolic defects is achieved by incubation of the Hunter syndrome macrophages in normal serum, demonstrating that the abnormal MPS II macrophages are responsive to exogenously supplied enzyme (α-L-iduronate sulfatase). Preliminary studies of MPS turnover in macrophages from two obligate MPS heterozygotes are indicative of partially impaired MPS degradation, with increased 35SO4 incorporation and a lower rate of 35SO4-MPS degradation.
Speculation: The human blood-derived macrophage system should be a useful one for the investigation of enzyme replacement and other modes of therapy for the lysosomal storage diseases.
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Yatziv, S., Epstein, L. & Epstein, C. Monocyte-derived Macrophages: An in Vitro System for Studying Hereditary Lysosomal Storage Diseases. Pediatr Res 12, 939–944 (1978). https://doi.org/10.1203/00006450-197809000-00011
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DOI: https://doi.org/10.1203/00006450-197809000-00011