Macrophages control tissue homeostasis via Ferritin heavy chain

• Autor(a) principal: Ventura, Pedro Manuel Oliveira
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/25658
• topic: Iron; FTH; Homeostasis; Macrophages; Domínio/Área Científica::Engenharia e Tecnologia::Outras Engenharias e Tecnologias

Due to its inherent capacity to catalyze reduction-oxidation reactions, iron is at the center stage of vital biological functions essential to most living organisms. Paradoxically, these same inherent characteristics are also responsible for the deleterious effects of iron. In the intracellular environment, iron is oxidized to its inert biological form by the ferroxidase activity of Ferritin Heavy Chain (FTH). In this Thesis we used a genetic loss of function approach in mice to demonstrate that FTH is essential to control the deleterious effects of iron and as such to maintain homeostasis in vivo. Namely we found that global deletion of the Fth allele is lethal in adult mice, an outcome prevented by the expression of FTH in macrophages. To investigate further the mechanisms by which FTH in macrophages contributes to maintain homeostasis we generated and characterized a genetically modified mouse strain in which FTH was tagged with a small V5 epitope. We found that contrary to what would be expected FTH is not secreted from macrophages to exert its protective effect. We conclude that FTH expression in macrophages acts in a cell autonomous manner to support homeostasis.