Human leukocyte glycosylasparaginase: cell-to-cell transfer and properties in correction of aspartylglycosaminuria

FEBS Lett. 2001 Jun 15;499(1-2):77-81. doi: 10.1016/s0014-5793(01)02526-1.

Abstract

Aspartylglycosaminuria (AGU), a severe lysosomal storage disease, is caused by the deficiency of the lysosomal enzyme, glycosylasparaginase (GA), and accumulation of aspartylglucosamine (GlcNAc-Asn) in tissues. Here we show that human leukocyte glycosylasparaginase can correct the metabolic defect in Epstein-Barr virus (EBV)-transformed AGU lymphocytes rapidly and effectively by mannose-6-phosphate receptor-mediated endocytosis or by contact-mediated cell-to-cell transfer from normal EBV-transformed lymphocytes, and that 2-7% of normal activity is sufficient to correct the GlcNAc-Asn metabolism in the cells. Cell-to-cell contact is obligatory for the transfer of GA since normal transformed lymphocytes do not excrete GA into extracellular medium. The combined evidence indicates that cell-to-cell transfer of GA plays a main role in enzyme replacement therapy of AGU by normal lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / analogs & derivatives
  • Acetylglucosamine / metabolism*
  • Aspartylglucosaminuria
  • Aspartylglucosylaminase / genetics
  • Aspartylglucosylaminase / metabolism*
  • Cell Line, Transformed
  • Coculture Techniques
  • Culture Media, Conditioned / metabolism
  • Endocytosis* / drug effects
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique
  • Herpesvirus 4, Human / physiology
  • Humans
  • Leukocytes / cytology
  • Leukocytes / drug effects
  • Leukocytes / enzymology*
  • Leukocytes / metabolism
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / enzymology
  • Lymphocytes / metabolism
  • Lysosomal Storage Diseases / enzymology*
  • Lysosomal Storage Diseases / genetics
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Mannosephosphates / metabolism
  • Mannosephosphates / pharmacology
  • Protein Transport / drug effects
  • Receptor, IGF Type 2 / metabolism
  • Y Chromosome / genetics

Substances

  • Culture Media, Conditioned
  • Mannosephosphates
  • Receptor, IGF Type 2
  • N-acetylglucosaminylasparagine
  • mannose-6-phosphate
  • Aspartylglucosylaminase
  • Acetylglucosamine