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Ferritin-mediated neutrophil extracellular traps formation and cytokine storm via macrophage scavenger receptor in sepsis-associated lung injury.
Zhang, Hao; Wu, Dan; Wang, Yanghanzhao; Shi, Yuxin; Shao, Yuwen; Zeng, Fu; Spencer, Charles B; Ortoga, Lilibeth; Wu, Dehua; Miao, Changhong.
Afiliação
  • Zhang H; Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180# Feng-Lin Road, Shanghai, 200032, China. zhang.hao@zs-hospital.sh.cn.
  • Wu D; Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China. zhang.hao@zs-hospital.sh.cn.
  • Wang Y; Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, China. zhang.hao@zs-hospital.sh.cn.
  • Shi Y; Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180# Feng-Lin Road, Shanghai, 200032, China.
  • Shao Y; Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China.
  • Zeng F; Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Spencer CB; Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180# Feng-Lin Road, Shanghai, 200032, China.
  • Ortoga L; Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai, China.
  • Wu D; Department of Anesthesiology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Miao C; Department of Anesthesiology, Zhongshan Hospital, Fudan University, 180# Feng-Lin Road, Shanghai, 200032, China.
Cell Commun Signal ; 22(1): 97, 2024 02 02.
Article em En | MEDLINE | ID: mdl-38308264
ABSTRACT

BACKGROUND:

Sepsis is a severe systemic inflammatory disorder manifested by a dysregulated immune response to infection and multi-organ failure. Numerous studies have shown that elevated ferritin levels exist as an essential feature during sepsis and are able to suggest patients' prognoses. At the same time, the specific mechanism of ferritin-induced inflammatory injury remains unclear.

METHODS:

Hyper-ferritin state during inflammation was performed by injecting ferritin into a mouse model and demonstrated that injection of ferritin could induce a systemic inflammatory response and increase neutrophil extracellular trap (NET) formation.Padi4-/-, Elane-/- and Cybb-/- mice were used for the NETs formation experiment. Western blot, immunofluorescence, ELISA, and flow cytometry examined the changes in NETs, inflammation, and related signaling pathways.

RESULTS:

Ferritin induces NET formation in a peptidylarginine deiminase 4 (PAD4), neutrophil elastase (NE), and reactive oxygen species (ROS)-dependent manner, thereby exacerbating the inflammatory response. Mechanistically, ferritin induces the expression of neutrophil macrophage scavenger receptor (MSR), which promotes the formation of NETs. Clinically, high levels of ferritin in patients with severe sepsis correlate with NETs-mediated cytokines storm and are proportional to the severity of sepsis-induced lung injury.

CONCLUSIONS:

In conclusion, we demonstrated that hyper-ferritin can induce systemic inflammation and increase NET formation in an MSR-dependent manner. This process relies on PAD4, NE, and ROS, further aggravating acute lung injury. In the clinic, high serum ferritin levels are associated with elevated NETs and worse lung injury, which suggests a poor prognosis for patients with sepsis. Our study indicated that targeting NETs or MSR could be a potential treatment to alleviate lung damage and systemic inflammation during sepsis. Video Abstract.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sepse / Lesão Pulmonar Aguda / Armadilhas Extracelulares Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Cell Commun Signal Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Sepse / Lesão Pulmonar Aguda / Armadilhas Extracelulares Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Revista: Cell Commun Signal Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China