Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages.
The expression of ferroportin1 (FPN1) in reticuloendothelial macrophages supports the hypothesis that this iron-export protein participates in iron recycling from senescent erythrocytes. To gain insight into FPN1's role in macrophage iron metabolism, we examined the effect of iron status and erythrophagocytosis on FPN1 expression in J774 macrophages. Northern analysis indicated that FPN1 mRNA levels decreased with iron depletion and increased on iron loading. The iron-induced induction of FPN1 mRNA was blocked by actinomycin D, suggesting that transcriptional control was responsible for this effect. After erythrophagocytosis, FPN1 mRNA levels were also up-regulated, increasing 8-fold after 4 hours and returning to basal levels by 16 hours. Western analysis indicated corresponding increases in FPN1 protein levels, with maximal induction after 10 hours. Iron chelation suppressed FPN1 mRNA and protein induction after erythrophagocytosis, suggesting that FPN1 induction results from erythrocyte-derived iron. Comparative Northern analyses of iron-related genes after erythrophagocytosis revealed a 16-fold increase in FPN1 levels after 3 hours, a 10-fold increase in heme oxygenase-1 (HO-1) after 3 hours, a 2-fold increase in natural resistance macrophage-associated protein 1 (Nramp1) levels after 6 hours, but no change in divalent metal ion transporter 1 (DMT1) levels. The rapid and strong induction of FPN1 expression after erythrophagocytosis suggests that FPN1 plays a role in iron recycling.
Knutson
Mitchell D
MD
Harvard School of Public Health, Dept of Nutrition, Bldg 2, Rm 205, 665 Huntington Ave, Boston, MA 02115, USA.
Vafa
Mohammad R
MR
Haile
David J
DJ
Wessling-Resnick
Marianne
M
D000818:Animals; D027682:Cation Transport Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004912:Erythrocytes / Q000737:chemistry; D005293:Ferritins / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D007501:Iron / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects; D000098742:Ferroportin
D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron