IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7332.html
   My bibliography  Save this article

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages

Author

Listed:
  • Manabu Ueno

    (Gunma University Graduate School of Medicine)

  • Toshitaka Maeno

    (Gunma University Graduate School of Medicine)

  • Satoshi Nishimura

    (Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, The University of Tokyo
    Jichi Medical University)

  • Fusa Ogata

    (Translational Systems Biology and Medicine Initiative, Graduate School of Medicine, The University of Tokyo
    Jichi Medical University)

  • Hiroaki Masubuchi

    (Gunma University Graduate School of Medicine)

  • Kenichiro Hara

    (Gunma University Graduate School of Medicine)

  • Kouichi Yamaguchi

    (Gunma University Graduate School of Medicine)

  • Fumiaki Aoki

    (Gunma University Graduate School of Medicine)

  • Tatsuo Suga

    (Gunma University Graduate School of Medicine)

  • Ryozo Nagai

    (Jichi Medical University)

  • Masahiko Kurabayashi

    (Gunma University Graduate School of Medicine)

Abstract

Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80+CD11bhighCD11cmild population characterizing inflammatory macrophages, and the F4/80+CD11bmildCD11chigh population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

Suggested Citation

  • Manabu Ueno & Toshitaka Maeno & Satoshi Nishimura & Fusa Ogata & Hiroaki Masubuchi & Kenichiro Hara & Kouichi Yamaguchi & Fumiaki Aoki & Tatsuo Suga & Ryozo Nagai & Masahiko Kurabayashi, 2015. "Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages," Nature Communications, Nature, vol. 6(1), pages 1-13, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7332
    DOI: 10.1038/ncomms7332
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7332
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms7332?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Gizem Günes Günsel & Thomas M. Conlon & Aicha Jeridi & Rinho Kim & Zeynep Ertüz & Niklas J. Lang & Meshal Ansari & Mariia Novikova & Dongsheng Jiang & Maximilian Strunz & Mariia Gaianova & Christine H, 2022. "The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD," Nature Communications, Nature, vol. 13(1), pages 1-21, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7332. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.