Iron metabolism of established human hematopoietic cell lines in vitro.
Three malignant hematopoietic cell lines were used in studies on cellular iron metabolism. Our results show that iron-carrying transferrin became bound to specific dimeric cell surface receptors. Iron accumulated within the cell with time, whereas intact transferrin was released back to the medium. Chloroquine and NH4Cl, known as pH-raising agents in vesicles of the lysosomal system, inhibited iron accumulation and transferrin binding in a dose-dependent manner. This suggests that the acid pH in endosomes leads to the cleavage of the iron-transferrin bonds. Transferrin degradation was not found, which leads us to suggest a process of 'acid flushing' for the dissociation of iron from transferrin without the involvement of endosome-lysosome fusion. Taken together, the data agree with the concept of receptor-mediated endocytosis, as described for many macromolecules. Iron was stored in ferritin in the cell types tested. Only a minor part (less than 15%) of the iron was bound in hemoglobin in the K-562 cell line. The relationship between iron stores and exogenously added iron in heme synthesis was investigated using a double labelling (55Fe/59Fe) technique. The results showed that exogenous iron was preferentially used before the iron stored in ferritin. The results are discussed in relation to various hypotheses on cellular iron uptake and transport.
D000643:Ammonium Chloride / Q000494:pharmacology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute; D008214:Lymphocytes / Q000378:metabolism*; D008223:Lymphoma; D008264:Macrophages / Q000378:metabolism*; D014168:Transferrin / Q000378:metabolism*
D014168:Transferrin; D000643:Ammonium Chloride; D006418:Heme; D002738:Chloroquine; D005293:Ferritins; D007501:Iron