Hfe deficiency impairs pulmonary neutrophil recruitment in response to inflammation

• Verfasst von: Gente, Karolina [VerfasserIn]
• Verfasst von: Spasić Vujić, Maja [VerfasserIn]
• Verfasst von: Schäfer, Sebastian Markus [VerfasserIn]
• Verfasst von: Stolte, Jens [VerfasserIn]
• Verfasst von: Baehr-Ivacevic, Tomi [VerfasserIn]
• Verfasst von: Waldow, Katharina [VerfasserIn]
• Verfasst von: Zhou-Suckow, Zhe [VerfasserIn]
• Verfasst von: Klingmüller, Ursula [VerfasserIn]
• Verfasst von: Benes, Vladimir [VerfasserIn]
• Verfasst von: Mall, Marcus A. [VerfasserIn]
• Verfasst von: Muckenthaler, Martina [VerfasserIn]
• Titel: Hfe deficiency impairs pulmonary neutrophil recruitment in response to inflammation
• Verf.angabe: Karolina Benesova, Maja Vujić Spasić, Sebastian M. Schaefer, Jens Stolte, Tomi Baehr-Ivacevic, Katharina Waldow, Zhe Zhou, Ursula Klingmueller, Vladimir Benes, Marcus A. Mall, Martina U. Muckenthaler
• E-Jahr: 2012
• Jahr: June 21, 2012
• Umfang: 12 S.
• Fussnoten: Gesehen am 09.04.2018
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2012
• Band/Heft Quelle: 7(2012,6) Artikel-Nummer e39363, 12 Seiten
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0039363
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Alveolar macrophages
• Sach-SW: Cytokines
• Sach-SW: Homeostasis
• Sach-SW: Inflammation
• Sach-SW: Inflammatory diseases
• Sach-SW: Iron deficiency
• Sach-SW: Macrophages
• Sach-SW: Neutrophils
• K10plus-PPN: 1571808183

Abstract

Regulation of iron homeostasis and the inflammatory response are tightly linked to protect the host from infection. Here we investigate how imbalanced systemic iron homeostasis in a murine disease model of hereditary hemochromatosis (Hfe−/− mice) affects the inflammatory responses of the lung. We induced acute pulmonary inflammation in Hfe−/− and wild-type mice by intratracheal instillation of 20 µg of lipopolysaccharide (LPS) and analyzed local and systemic inflammatory responses and iron-related parameters. We show that in Hfe−/− mice neutrophil recruitment to the bronchoalveolar space is attenuated compared to wild-type mice although circulating neutrophil numbers in the bloodstream were elevated to similar levels in Hfe−/− and wild-type mice. The underlying molecular mechanisms are likely multifactorial and include elevated systemic iron levels, alveolar macrophage iron deficiency and/or hitherto unexplored functions of Hfe in resident pulmonary cell types. As a consequence, pulmonary cytokine expression is out of balance and neutrophils fail to be recruited efficiently to the bronchoalveolar compartment, a process required to protect the host from infections. In conclusion, our findings suggest a novel role for Hfe and/or imbalanced iron homeostasis in the regulation of the inflammatory response in the lung and hereditary hemochromatosis.