Regulation of phagosomal iron release from murine macrophages by nitric oxide.
The role of NO in macrophage iron turnover was studied in macrophages from inducible nitric oxide synthase (iNOS)-deficient mice. Interferon gamma/lipopolysaccharide (IFNgamma/LPS)-activated bone marrow-derived macrophages from iNOS-deficient mice, following phagocytosis of 59Fe-labelled transferrin-anti-transferrin immune complexes, showed reduced iron release compared with cells from wild-type iNOS littermates. Uptake of the complexes by macrophages was similar in iNOS-deficient and wild-type mice. Ferritin was up-regulated by IFNgamma/LPS treatment, but NO exercised a modest opposing down-regulatory effect. No effect of iNOS deficiency was seen when iron was taken up from iron citrate, which enters via a non-phagocytic route. These results suggest that NO plays a key role in regulating iron turnover in macrophages acquiring iron by phagocytosis of erythrocytes or cell debris, and thus the supply to peripheral tissues, such as to the bone marrow for erythropoiesis.
Mulero
Victoriano
V
Department of Immunology and Bacteriology, Western Infirmary, University of Glasgow, Glasgow, UK. vmulero@um.es
Wei
Xiao-qing
XQ
Liew
Foo Y
FY
Brock
Jeremy H
JH
D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism; D002478:Cells, Cultured; D005290:Ferric Compounds / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010588:Phagosomes / Q000187:drug effects* / Q000378:metabolism*; D014168:Transferrin / Q000276:immunology / Q000378:metabolism
D000936:Antigen-Antibody Complex; D005290:Ferric Compounds; D014168:Transferrin; D009569:Nitric Oxide; C025314:ferric citrate; D005293:Ferritins; D007501:Iron; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse