Regulation of phagosomal iron release from murine macrophages by nitric oxide

Abstract

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.

In Vivo Detection of Macrophages in Human Carotid Atheroma

“…We think this most likely represents a "washout" of iron particles from the plaque by diffusion or by physiological recirculation of the endocytosed iron, 14 which would be supported by the relative increase in rSI measured after 48 hours. Despite an average time interval between USPIO infusion and surgery of less than 7 days, there was a wide range (up to 18 days) because of pressures on the operating department, which made the relationship between MRI signal effect and USPIO accumulation difficult to interpret.…”

Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis

“…The latter observation suggests potential defects in iron release, which also impedes the course of erythropoiesis. 37 However, we did not find altered expression of the ironregulating hormone hepcidin 38 in the liver of CD70TG mice (supplemental Figure 2a-b), indicating that hepcidin is not causally involved in the anemic phenotype of these mice.…”

The Effect of the Host’s Iron Status on Tuberculosis

“…First, during experimental TB, alternatively activated mouse macrophages express the gene encoding arginase-1 [41]. Arginase-1 competition with inducible nitric oxide synthase (iNOS) for l-arginine results in decreased NO production and, hence, possibly less iron efflux [42] and more iron being available to M. tuberculosis. Whether the differential expression of arginase-1 versus iNOS applies to humans is unclear.…”