Antibody-mediated targeting of alpha-1,4-glucosidase-albumin polymers to rat hepatocytes. A model for enzyme therapy.
Chemically cross-linking alpha-1,4-glucosidase, homologous albumin and antibody (immunoglobulin G, IgG) molecules raised against isolated rat hepatocytes yields an active and stable soluble enzyme-polymer complex of mol.wt. approx. 10(6). After intravenous injection, the 125I-labelled complex is seen to be preferentially associated with hepatocytes when compared with labelled free alpha-1,4-glucosidase, enzyme-albumin polymers without IgG or polymer linked to a non-specific IgG molecule, all of which are associated to a much larger extent with the Kupffer cells. The procedure offers several advantages for targeting of enzymes to specific tissues and cells and for the possible lowering of hepatocyte glycogen content in Type II glycogenesis (Pompe's disease).
D000818:Animals; D005959:Glucosidases / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000008:administration & dosage*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008954:Models, Biological; D008970:Molecular Weight; D051381:Rats; D012709:Serum Albumin / Q000008:administration & dosage / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects; D000520:alpha-Glucosidases / Q000008:administration & dosage / Q000494:pharmacology*
D007074:Immunoglobulin G; D012709:Serum Albumin; D005959:Glucosidases; C024982:alpha-1,4-glucosidase-albumin polymer; D000520:alpha-Glucosidases