Selective uptake of ricin A-chain by hepatic non-parenchymal cells in vitro. Importance of mannose oligosaccharides in the toxin.
Free ricin A-chain was actively taken up in vitro by rat liver non-parenchymal cells but not by parenchymal cells. A-chain uptake by non-parenchymal cells could be selectively inhibited by D-mannose, L-fucose or ovalbumin and was markedly decreased after partial removal of mannose residues from the oligosaccharides present in the glycoprotein by enzymic deglycosylation. Uptake of free ricin B-chain by non-parenchymal cells was greater than that by parenchymal cells but in both cases was little influenced by enzymic deglycosylation of the glycoprotein. The results are consistent with mannose receptor recognition of ricin A-chain by non-parenchymal cells and have important implications for the clinical use in vivo of antibody-ricin A-chain conjugates in cancer therapy.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005643:Fucose / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008358:Mannose / Q000378:metabolism / Q000494:pharmacology; D009844:Oligosaccharides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012276:Ricin / Q000378:metabolism*
D009844:Oligosaccharides; D005643:Fucose; D012276:Ricin; D008358:Mannose