Multivalent metal-induced iron acquisition from transferrin and lactoferrin by myeloid cells.
We previously described a unique, high-capacity, ATP-independent mechanism through which myeloid cells acquire Fe from low-m.w. chelates. The rate of this Fe acquisition is markedly increased by cellular exposure to multivalent metal cations. Because most Fe in vivo is bound to transferrin or lactoferrin, we examined whether this mechanism also contributes to myeloid cell acquisition of Fe from transferrin and/or lactoferrin. Using HL-60 cells as a model system, we show cellular acquisition of (59)Fe from both lactoferrin and transferrin that was unaffected by conditions that depleted the cells of ATP or disrupted their cytoskeleton. Fe acquisition was dramatically increased by cell exposure to various metals including Ga(3+), Gd(3+), Al(3+), Fe(3+), La(3+), Zr(4+), Sn(4+), Cu(2+), and Zn(2+) by a process that was reversible. Exposure to these same metals also increased binding of both transferrin and lactoferrin to the cell surface by a process that does not appear to involve the well-described plasma membrane receptor for transferrin. Approximately 60% of the Fe acquired by the cells from transferrin and lactoferrin remained cell associated 18 h later. HL-60 cells possess a high-capacity multivalent metal-inducible mechanism for Fe acquisition from transferrin and lactoferrin that bears many similarities to the process previously described that allows these and other cell types to acquire Fe from low-m.w. Fe chelates. The biologic importance of this mechanism may relate to its high Fe acquisition capacity and the speed with which it is able to rapidly adapt to the level of extracellular Fe.
Olakanmi
Oyebode
O
Department of. Internal Medicine, Veterans Affairs Medical Center, Iowa City, IA 52246, USA.
Rasmussen
George T
GT
Lewis
Troy S
TS
Stokes
John B
JB
Kemp
John D
JD
Britigan
Bradley E
BE
D000255:Adenosine Triphosphate / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002412:Cations / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004705:Endocytosis; D005708:Gallium / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007781:Lactoferrin / Q000378:metabolism*; D008670:Metals / Q000494:pharmacology*; D011990:Receptors, Transferrin / Q000187:drug effects / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism*
D002412:Cations; D002614:Chelating Agents; D008670:Metals; D011990:Receptors, Transferrin; D014168:Transferrin; D000255:Adenosine Triphosphate; D005708:Gallium; D007501:Iron; D007781:Lactoferrin