Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor

Junichi Nishimura, Hiroyuki Saiga, Shintaro Sato, Megumi Okuyama, Hisako Kayama, Hirotaka Kuwata, Sohkichi Matsumoto, Toshirou Nishida, Yoshiki Sawa, Shizuo Akira, Yasunobu Yoshikai, Masahiro Yamamoto, Kiyoshi Takeda

    Research output: Contribution to journalArticle

    31 Citations (Scopus)

    Abstract

    Secretory leukocyte protease inhibitor (SLPI) has multiple functions, including inhibition of protease activity, microbial growth, and inflammatory responses. In this study, we demonstrate that mouse SLPI is critically involved in innate host defense against pulmonary mycobacterial infection. During the early phase of respiratory infection with Mycobacterium bovis bacillus Calmette-Guérin, SLPI was produced by bronchial and alveolar epithelial cells, as well as alveolar macrophages, and secreted into the alveolar space. Recombinant mouse SLPI effectively inhibited in vitro growth of bacillus Calmette-Guérin and Mycobacterium tuberculosis through disruption of the mycobacterial cell wall structure. Each of the two whey acidic protein domains in SLPI was sufficient for inhibiting mycobacterial growth. Cationic residues within the whey acidic protein domains of SLPI were essential for disruption of mycobacterial cell walls. Mice lacking SLPI were highly susceptible to pulmonary infection with M. tuberculosis. Thus, mouse SLPI is an essential component of innate host defense against mycobacteria at the respiratory mucosal surface.

    Original languageEnglish
    Pages (from-to)4032-4039
    Number of pages8
    JournalJournal of Immunology
    Volume180
    Issue number6
    DOIs
    Publication statusPublished - Mar 15 2008

    All Science Journal Classification (ASJC) codes

    • Immunology

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  • Cite this

    Nishimura, J., Saiga, H., Sato, S., Okuyama, M., Kayama, H., Kuwata, H., Matsumoto, S., Nishida, T., Sawa, Y., Akira, S., Yoshikai, Y., Yamamoto, M., & Takeda, K. (2008). Potent antimycobacterial activity of mouse secretory leukocyte protease inhibitor. Journal of Immunology, 180(6), 4032-4039. https://doi.org/10.4049/jimmunol.180.6.4032