Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses

Zhuzhen Zhang, Fan Zhang, Peng An, Xin Guo, Yuanyuan Shen, Yunlong Tao, Qian Wu, Yuchao Zhang, Yu Yu, Bo Ning, Guangjun Nie, Mitchell D. Knutson, Gregory J. Anderson, Fudi Wang

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Systemic iron requirements are met predominantly through the recycling of iron from senescent erythrocytes by macrophages a process in which the iron exporter ferroportin (Fpn1) is considered to be essential. Yet the role of Fpn1 in macrophage iron recycling and whether it influences innate immune responses are poorly understood in vivo.We inactivated Fpn1 in macrophages by crossing Fpn1- floxed animals with macrophage-targeted LysM-Cre or F4/80-Cre transgenic mice. Macrophage Fpn1 deletion mice were overtly normal however they displayed a mild anemia and iron accumulation in splenic hepatic and bone marrow macrophages when fed a standard diet. Iron loading was exacerbated after the administration of iron dextran or phenylhydrazine. When Fpn1LysM/LysM mice were challenged with an iron-deficient diet they developed a more severe anemia and strikingly higher splenic iron levels than control mice indicating significantly impaired iron mobilization from macrophages. Because immune responses can be altered by modulating iron status we also examined the expression of proinflammatory cytokines. We found that expression levels of TNF-α and IL-6 were significantly enhanced in Fpn1LysM/LysM macrophages lacking Fpn1. These studies demonstrate that Fpn1 plays important roles in macrophage iron release in vivo and in modulating innate immune responses.

Original languageEnglish (US)
Pages (from-to)1912-1922
Number of pages11
JournalBlood
Volume118
Issue number7
DOIs
StatePublished - Aug 18 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Zhang, Z., Zhang, F., An, P., Guo, X., Shen, Y., Tao, Y., Wu, Q., Zhang, Y., Yu, Y., Ning, B., Nie, G., Knutson, M. D., Anderson, G. J., & Wang, F. (2011). Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses. Blood, 118(7), 1912-1922. https://doi.org/10.1182/blood-2011-01-330324