Blood, 1 May 2001, Vol. 97, No. 9, pp. 2734-2740
IMMUNOBIOLOGY
Iron transport in a lymphoid cell line with the hemochromatosis
C282Y mutation
Christopher R. Chitambar and
Janine P. Wereley
From the Division of Hematology/Oncology, Department of
Medicine, Medical College of Wisconsin, Milwaukee, WI.
The gene for hemochromatosis (HFE) is
expressed in a variety of cells, including those not thought to be
affected by this disease. The impact of HFE on iron
transport was examined in B-lymphoid cell lines developed from a
patient with hemochromatosis with the HFE C282Y mutation
(C282Y cells) and an individual with the wild-type HFE gene
(WT cells). Whereas both cell lines expressed HFE protein, C282Y cells
displayed less HFE protein at the cell surface. Transferrin receptor
(TfR) number was 2- to 3-fold greater in WT cells than in C282Y cells,
while TfR affinity for transferrin (Tf) was slightly lower in C282Y
cells. TfR distribution between intracellular and cell-surface
compartments was similar in both cell lines. Iron uptake per cell was
greater in WT cells but was not increased proportional to TfR number.
When considered relative to cell-surface TfR number, however, iron
uptake and Tf internalization were actually greater in C282Y cells.
Surprisingly, Tf-independent iron uptake was also significantly greater
in C282Y cells than in WT cells. The ferritin content of C282Y cells
was approximately 40% that of WT cells. Exposure of cells to
pro-oxidant conditions in culture led to a greater inhibition of
proliferation in C282Y cells than in WT cells. Our results indicate
that in this B-lymphoid cell line, the HFE C282Y mutation
affects both Tf-dependent and -independent iron uptake and enhances
cell sensitivity to oxidative stress. The role of HFE in
iron uptake by B cells may extend beyond its known interaction with the TfR.
