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Therefore, iron acquisition, transport, storage, and release are tightly regulated, by several important proteins. Cytosolic ferritin is an iron storage protein composed of 24 subunits of either the L- or the H-type chains. H-ferritin differs from L-ferritin in the capacity to oxidize Fe<jats:sup>2+<\/jats:sup> to Fe<jats:sup>3+<\/jats:sup>. In this work, we investigated the role played by H-ferritin in the macrophages\u2019 ability to respond to immune stimuli and to deal with exogenously added iron. We used mice with a conditional deletion of the H-ferritin gene in the myeloid lineage to obtain bone marrow-derived macrophages. These macrophages had normal viability and gene expression under basal culture conditions. However, when treated with interferon-gamma and lipopolysaccharide they had a lower activation of Nitric Oxide Synthase 2. Furthermore, H-ferritin-deficient macrophages had a higher sensitivity to iron-induced toxicity. This sensitivity was associated with a lower intracellular iron accumulation but a higher production of reactive oxygen species. These data indicate that H-ferritin modulates macrophage response to immune stimuli and that it plays an essential role in protection against iron-induced oxidative stress and cell death.<\/jats:p>","DOI":"10.1038\/s41598-020-59898-0","type":"journal-article","created":{"date-parts":[[2020,2,20]],"date-time":"2020-02-20T11:03:11Z","timestamp":1582196591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["H-Ferritin is essential for macrophages\u2019 capacity to store or detoxify exogenously added iron"],"prefix":"10.1038","volume":"10","author":[{"given":"Gon\u00e7alo","family":"Mesquita","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6087-1487","authenticated-orcid":false,"given":"T\u00e2nia","family":"Silva","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5305-8538","authenticated-orcid":false,"given":"Ana C.","family":"Gomes","sequence":"additional","affiliation":[]},{"given":"Pedro F.","family":"Oliveira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7635-783X","authenticated-orcid":false,"given":"Marco G.","family":"Alves","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9535-368X","authenticated-orcid":false,"given":"Rui","family":"Fernandes","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1297-3198","authenticated-orcid":false,"given":"Agostinho A.","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Ana C.","family":"Moreira","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7657-2118","authenticated-orcid":false,"given":"Maria Salom\u00e9","family":"Gomes","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,2,20]]},"reference":[{"key":"59898_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0098-2997(00)00006-6","volume":"22","author":"PT Lieu","year":"2001","unstructured":"Lieu, P. 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