Cargando…

Macrophage ferroportin serves as a therapeutic target against bacteria-induced acute lung injury by promoting barrier restoration

Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were chara...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Hanbin, Zeng, Congli, Luo, Gan, Sun, Yaqi, Zhang, Jue, Xu, Zhipeng, Guo, Yuqian, Ye, Hui, Mao, Jiali, Chen, Shiyu, Zhang, Yan, Zhang, Kai, Vidal Melo, Marcos F., Fang, Xiangming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9768356/
https://www.ncbi.nlm.nih.gov/pubmed/36567719
http://dx.doi.org/10.1016/j.isci.2022.105698
Descripción
Sumario:Acute respiratory distress syndrome (ARDS) is a common lung disorder that involves severe inflammatory damage in the pulmonary barrier, but the underlying mechanisms remain elusive. Here, we demonstrated that pulmonary macrophages originating from ARDS patients and mice caused by bacteria were characterized by increased expression of ferroportin (FPN). Specifically deleting FPN in myeloid cells conferred significant resistance to bacterial infection with improved survival by decreasing extracellular bacterial growth and preserving pulmonary barrier integrity in mice. Mechanistically, macrophage FPN deficiency not only limited the availability of iron to bacteria, but also promoted tissue restoration via growth factor amphiregulin, which is regulated by cellular iron-activated Yes-associated protein signaling. Furthermore, pharmacological treatment with C-Hep, the self-assembled N-terminally cholesterylated minihepcidin that functions in the degradation of macrophage FPN, protected against bacteria-induced lung injury. Therefore, therapeutic strategies targeting the hepcidin-FPN axis in macrophages may be promising for the clinical treatment of acute lung injury.