MONOCYTE-DERIVED MACROPHAGES - INVITRO SYSTEM FOR STUDYING HEREDITARY LYSOSOMAL STORAGE DISEASES

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-acetyl glucosaminidase, is reached by the seventh day in culture. The rate of35SO4 incorporation into mucopolysaccharides is also maximal at 7 days. Normal macrophages attain a steady state of35SO4 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 more35SO4 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 increased35SO4 incorporation and a lower rate of35SO4-MPS degradation. © 1978 International Pediatric Research Foundation, Inc.