In vivo behaviour of rat transferrin bearing a hybrid glycan and its interaction with macrophages.
Production of rat transferrin containing a single hybrid glycan was induced by treating rats with swainsonine, an inhibitor of alpha-mannosidase II. The principal component of this variant transferrin containing one sialic acid residue per mole of protein was separated from other forms of transferrin by anion-exchange chromatography, followed by lectin affinity chromatography. Transferrin bearing the hybrid glycan was degraded in vivo with a half-life of 14 h as compared with 40 h for transferrin containing a standard diantennary glycan. By using 125I-labelled tyramine-cellobiose, a label whose discharge from lysosomes is strongly retarded, organs rich in reticuloendothelial elements (liver, bone marrow, lungs, and spleen) were identified as the major sites of catabolism of the transferrin variant. The liver took up more 59Fe from the variant (26% of the dose in 90 min) than from control rat transferrin (12%). The excess iron uptake was reduced by the intravenous injection of either human transferrin or ovalbumin, and it was abolished by administering both. Macrophages from bone marrow and lungs degraded the transferrin variant in vitro. The degradation was significantly enhanced when transferrin receptors were blocked by human transferrin, and it was significantly reduced by ovalbumin and methyl glucopyranoside.
Hu
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WL
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ont., Canada.
Chindemi
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PA
Regoeczi
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E
D000818:Animals; D002848:Chromatography, DEAE-Cellulose; D006031:Glycosylation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008361:Mannosidases / Q000037:antagonists & inhibitors; D019158:N-Acetylneuraminic Acid; D011134:Polysaccharides / Q000737:chemistry*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000378:metabolism; D012794:Sialic Acids / Q000737:chemistry; D017026:Swainsonine / Q000494:pharmacology; D014168:Transferrin / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D043323:alpha-Mannosidase
D011134:Polysaccharides; D011990:Receptors, Transferrin; D012794:Sialic Acids; D014168:Transferrin; D008361:Mannosidases; D043323:alpha-Mannosidase; D019158:N-Acetylneuraminic Acid; D017026:Swainsonine