Transferrin receptor-dependent and -independent iron transport in gallium-resistant human lymphoid leukemic cells

Recent studies showed that gallium and iron uptake are decreased in gallium-resistant (R) CCRF-CEM cells; however, the mechanisms involved were not fully elucidated. In the present study, we compared the cellular uptake of (59)Fetransferrin (Tf) and Fe-59-pyridoxal isonicotinoyl hydrazone (PIH) to determine whether the decrease in iron uptake by R cells is caused by changes in Tf receptor (TfR)-dependent or TfR-independent iron uptake. We found that both Fe-59-Tf and Fe-59-PIH uptake were decreased in R cells. The uptake of Fe-59-Tf but not Fe-59-PIH could be blocked by an anti-TfR monoclonal antibody. After Fe-59-Tf uptake, R cells released greater amounts of Fe-59 than gallium-sensitive (s) cells. However, after Fe-59-PIH uptake Fe-59 release from S and R cells was similar. I-125=Tf exocytosis was greater in R cells. At confluency, S and R cells expressed equivalent amounts of TfR; however, at 24 and 48 hours in culture, TfR expression was lower in R cells. Our study suggests that the decrease in Tf-Fe uptake by R cells is caused by a combination of enhanced iron efflux from cells and decreased TfR-mediated iron transport into cells. Furthermore, because TfR-dependent and -independent iron uptake is decreased in R cells, both uptake systems may be controlled at some level by similar regulatory signal(s). (C) 1998 by The American Society of Hematology.