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Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by nonviable Candida albicans

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Abstract

Objective

This study aimed to evaluate the effect of myeloperoxidase (MPO) deficiency on lung inflammation induced by nonviable Candida albicans (nCA).

Methods

Mice were inoculated intranasally with nCA, and accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid was analyzed by flow cytometry. The levels of macrophage inflammatory protein 2 (MIP-2), keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β in the lung were measured by ELISA. Production of MIP-2 and KC from neutrophils and macrophages was quantified in vitro. MIP-2 mRNA expression in the neutrophils was analyzed by real-time reverse transcription-PCR, and the extent of phosphorylation of ERK1/2 and Syk in the neutrophils was analyzed by Western blotting.

Results

The MPO−/− mice that received nCA showed more severe pneumonia than wild-type mice. Within 12 h of nCA administration, MPO−/− mice had significantly higher numbers of alveolar neutrophils and increased production of MIP-2 and KC relative to the responses seen in wild-type mice. Neutralization of MIP-2 and KC in vivo significantly reduced neutrophil infiltration. In vitro, production of MIP-2, but not that of KC, was enhanced in the nCA-stimulated neutrophils from MPO−/− mice, concomitant with up-regulation of Syk and ERK1/2. At 1 and 3 days after nCA administration, MPO−/− mice had significantly higher lung concentrations of TNF-α and IL-1β than wild-type mice.

Conclusion

Pulmonary administration of nCA produced an altered inflammatory response in MPO−/− mice relative to wild-type mice. Enhanced MIP-2 production by MPO−/− neutrophils may at least partly contribute to exacerbated inflammation in mutant mice.

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Acknowledgments

We thank Minami Sugimura for technical support. This work was supported in part by JSPS KAKENHI Grant number 23580406, and 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

    Mizuki Homme, Nao Tateno & Yasuaki Aratani

  2. Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Noriko Miura & Naohito Ohno

Authors
  1. Mizuki Homme
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  2. Nao Tateno
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  3. Noriko Miura
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  5. Yasuaki Aratani
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Correspondence to Yasuaki Aratani.

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Responsible Editor: Mauro Teixeira.

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Homme, M., Tateno, N., Miura, N. et al. Myeloperoxidase deficiency in mice exacerbates lung inflammation induced by nonviable Candida albicans . Inflamm. Res. 62, 981–990 (2013). https://doi.org/10.1007/s00011-013-0656-6

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  • DOI: https://doi.org/10.1007/s00011-013-0656-6

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