PCBP2 Regulates Macrophage Iron Recycling and Erythropoiesis in Mice

Macrophages recycle iron from senescent erythrocytes, but the intracellular pathways governing its redistribution remain incompletely understood. A mechanistic study in Blood examined the role of the iron chaperone poly(rC)-binding protein 2 (PCBP2), using mice lacking PCBP2 in macrophages and profiling splenic cell subsets. The investigators also reported that iron deficiency induced PCBP2 expression in both mouse and human macrophages.

Mice with macrophage PCBP2 deficiency developed reduced bone marrow iron, altered peripheral erythrocytes and suppressed hepcidin levels, despite accumulating iron in the spleen. In splenic red pulp macrophages, PCBP2 depletion increased intracellular iron while reducing its bioavailability. The investigators attributed this pattern to impaired iron trafficking, with a smaller metabolically accessible iron pool and greater sequestration in ferritin. They also found evidence that PCBP2 is required for heme degradation and subsequent iron release.

The findings link macrophage iron trafficking to systemic iron availability and erythropoietic adaptation. PCBP2-dependent iron flux also protected iron-recycling macrophages from iron overload and oxidative stress during iron excess. These results offer mechanistic insight rather than evidence for a clinical intervention. Only the abstract was available; sample sizes, quantitative effect estimates and detailed methods were not reported in the supplied material.