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Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan

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Abstract

Objective and design

This study examines the role of myeloperoxidase (MPO), a major constituent of neutrophils that generates hypochlorous acid, in neutrophil recruitment into the zymosan-exposed lung of mice.

Methods

Mice were inoculated intranasally with zymosan. The accumulation of neutrophils and other inflammatory cells within the lung was analyzed by flow cytometry. Macrophage inflammatory protein 2 (MIP-2) expression in the lung was quantified, and the contribution of this chemokine to neutrophil accumulation was examined by intranasal administration of MIP-2 antibody. The cellular sources of MIP-2 were identified, and the production of this chemokine from macrophages and neutrophils was quantified in vitro.

Results

Zymosan exposure led to greater neutrophil infiltration into the lungs of MPO−/− mice relative to wild-type mice. This was associated with higher MIP-2 levels in the mutant mice. Neutralization of MIP-2 in vivo significantly reduced neutrophil infiltration. Neutrophils from MPO−/− mice produced more MIP-2, and the production was reduced when MPO was added exogenously.

Conclusions

MPO deficiency results in severe lung inflammation in mice exposed to zymosan. Relatively high MIP-2 levels likely contribute to the strong inflammatory response in these animals.

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Acknowledgments

We thank Akiko Okawara and Haruki Seta for technical support. We also thank Youichi Masuda and Yukari Nishitani for animal care. This work was supported in part by a Grant from the Japanese Ministry of Health, Labor, and Welfare.

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Authors and Affiliations

  1. Graduate School of Nanobioscience, Yokohama City University, Seto 22-2, Kanazawa, Yokohama, 236-0027, Japan

    Kazuhiro Takeuchi, Yu Umeki, Noriko Matsumoto, Kei Yamamoto, Mina Yoshida & Yasuaki Aratani

  2. Inflammation Program, Department of Immunology, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo, Chiba, 260-8670, Japan

    Kazuo Suzuki

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  1. Kazuhiro Takeuchi
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  2. Yu Umeki
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  3. Noriko Matsumoto
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  4. Kei Yamamoto
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  5. Mina Yoshida
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  6. Kazuo Suzuki
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  7. Yasuaki Aratani
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Correspondence to Yasuaki Aratani.

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Responsible Editor: Michael Parnham.

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Takeuchi, K., Umeki, Y., Matsumoto, N. et al. Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan. Inflamm. Res. 61, 197–205 (2012). https://doi.org/10.1007/s00011-011-0401-y

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  • DOI: https://doi.org/10.1007/s00011-011-0401-y

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