Cr. Chitambar et Jp. Wereley, TRANSFERRIN RECEPTOR-DEPENDENT AND RECEPTOR-INDEPENDENT IRON TRANSPORT IN GALLIUM-RESISTANT HUMAN LYMPHOID LEUKEMIC-CELLS, Blood, 91(12), 1998, pp. 4686-4693
Recent studies showed that gallium and iron uptake are decreased in ga
llium-resistant (R) CCRF-CEM cells; however, the mechanisms involved w
ere not fully elucidated. In the present study, we compared the cellul
ar 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-indep
endent iron uptake. We found that both Fe-59-Tf and Fe-59-PIH uptake w
ere decreased in R cells. The uptake of Fe-59-Tf but not Fe-59-PIH cou
ld be blocked by an anti-TfR monoclonal antibody. After Fe-59-Tf uptak
e, 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 ce
lls was similar. I-125=Tf exocytosis was greater in R cells. At conflu
ency, S and R cells expressed equivalent amounts of TfR; however, at 2
4 and 48 hours in culture, TfR expression was lower in R cells. Our st
udy 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-me
diated iron transport into cells. Furthermore, because TfR-dependent a
nd -independent iron uptake is decreased in R cells, both uptake syste
ms may be controlled at some level by similar regulatory signal(s). (C
) 1998 by The American Society of Hematology.