H-Ferritin is essential for macrophages' capacity to store or detoxify exogenously added iron

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

Mesquita, G (Autor) Outra; Silva, T (Autor) Outra; Gomes, AC (Autor) Outra; Oliveira, PF (Autor) FMUP; Alves, MG (Autor) Outra; Fernandes, R (Autor) Outra; Agostinho Almeida (Autor) FFUP; Moreira, AC (Autor) Outra; Gomes, MS (Autor) ICBAS

Revista

Título: Scientific Reports

Vol. 10

ISSN: 2045-2322

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 40 Citações

Scopus - 39 Citações

Outras Informações

ID Authenticus: P-00R-R16

DOI: 10.1038/s41598-020-59898-0

Abstract (EN): Macrophages are central cells both in the immune response and in iron homeostasis. Iron is both essential and potentially toxic. 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 Fe2+ to Fe3+. In this work, we investigated the role played by H-ferritin in the macrophages' 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 15