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. © 2012 Benesova et al.
CITATION STYLE
Benesova, K., Spasić, M. V., Schaefer, S. M., Stolte, J., Baehr-Ivacevic, T., Waldow, K., … Muckenthaler, M. U. (2012). Hfe deficiency impairs pulmonary neutrophil recruitment in response to inflammation. PLoS ONE, 7(6). https://doi.org/10.1371/journal.pone.0039363
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