Pulmonary Iron Homeostasis in Hepcidin Knockout Mice

Area of Science:

• Pulmonary medicine
• Iron metabolism
• Immunology

Background:

• Pulmonary iron excess can cause inflammation and disease.
• Lung iron homeostasis relies on regulating iron transport and storage.
• The iron hormone hepcidin is present in the lung.

Purpose of the Study:

• To investigate the role of lung hepcidin in pulmonary iron balance.
• To understand interactions between iron molecules and the hepcidin-ferroportin axis in the lung.
• To examine lung physiology and inflammation in systemic iron-loading models.

Main Methods:

• Utilized hepcidin knock-out (Hepc KO) and liver-specific hepcidin knock-out (Hepc KOliv) mouse models.
• Analyzed pulmonary iron levels, cellular iron uptake, and ferroportin expression.
• Assessed iron accumulation in alveolar macrophages and ferritin production.
• Investigated responses to intraperitoneal and intranasal LPS injections.

Main Results:

• Hepc KO mice showed increased pulmonary iron, cellular uptake, and apical ferroportin.
• Alveolar macrophages accumulated iron with elevated ferritin, unlike splenic/hepatic macrophages.
• Pulmonary hepcidin was not critical for local iron homeostasis; Hepc KOliv mice mirrored Hepc KO findings.
• High lung iron did not exacerbate acute lung inflammation or injury.
• Intranasal LPS, but not intraperitoneal LPS, induced pulmonary hepcidin, likely from alveolar macrophages.

Conclusions:

• Lung hepcidin is not essential for preventing pulmonary iron overload.
• Alveolar macrophages play a role in lung iron handling and hepcidin response.
• Pulmonary iron overload in this model does not inherently increase acute lung injury.
• Local lung hepcidin induction by inflammation depends on the route of challenge.