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

Nature Communications
Manabu UenoMasahiko Kurabayashi

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(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) 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 therapeu...Continue Reading

References

Jan 1, 1992·Bone·S E PapapoulosP Vermeij
Oct 1, 1990·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·M G Cecchini, H Fleisch
Jan 1, 1986·The American Review of Respiratory Disease·G L SniderP J Stone
Oct 1, 1995·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·D E HughesB F Boyce
Apr 29, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·S P LuckmanM J Rogers
Oct 1, 1998·The American Journal of Physiology·S BretonD Brown
Apr 22, 1999·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·N MakkonenJ Mönkkönen
May 26, 1999·American Journal of Respiratory Cell and Molecular Biology·S D Shapiro, R M Senior
Nov 11, 1999·American Journal of Respiratory and Critical Care Medicine·S D Shapiro
Jun 10, 2000·Chest·S D Shapiro
Aug 14, 2001·American Journal of Respiratory and Critical Care Medicine·I RetamalesJ C Hogg
May 16, 2002·Chest·Robert A Stockley
Sep 3, 2002·American Journal of Respiratory and Critical Care Medicine·Katsuyuki TomitaIan M Adcock
Oct 8, 2003·Current Pharmaceutical Design·Michael J Rogers
Oct 30, 2003·The European Respiratory Journal·P J BarnesR A Pauwels
Dec 3, 2003·American Journal of Respiratory Cell and Molecular Biology·Davey L PoelmaJ Freek van Iwaarden
Jan 13, 2004·Methods in Enzymology·Nico van Rooijen, Esther van Kesteren-Hendrikx
Dec 17, 2004·Pharmacological Reviews·Peter J Barnes
Jun 1, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·James E DunfordFraser P Coxon
Jun 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Toshitaka MaenoSteven D Shapiro
Mar 15, 2011·Journal of Controlled Release : Official Journal of the Controlled Release Society·Letícia CruzNicolas Tsapis
Jul 30, 2011·American Journal of Respiratory and Critical Care Medicine·Juan P de TorresBartolome R Celli
Jun 13, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mubing DuanMargaret L Hibbs

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Citations

Jan 5, 2016·Journal of Biomechanics·Jessica M OakesJosué Sznitman
Mar 18, 2016·Immunity·Thomas A Wynn, Kevin M Vannella
Dec 31, 2016·Pharmaceutics·Blessing AderibigbePatricia Popoola
Dec 14, 2016·Annual Review of Physiology·Kevin M Vannella, Thomas A Wynn
Feb 22, 2018·International Journal of Molecular Sciences·Kei Yamasaki, Stephan F van Eeden
Sep 15, 2018·Aging Cell·Audrey GriveauDavid Bernard
Apr 27, 2019·Expert Opinion on Therapeutic Patents·Sarah A Holstein
Jul 3, 2019·Assay and Drug Development Technologies·Hermann A M Mucke
Mar 21, 2020·Biomolecules·Ryuta MikawaMasataka Sugimoto
Dec 14, 2019·American Journal of Respiratory and Critical Care Medicine·Matthew HenkelBrian T Campfield
Feb 6, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hanbyeol LeeSe-Ran Yang
Aug 1, 2020·Journal of Cellular and Molecular Medicine·Yang YeQian Wang
Apr 1, 2017·American Journal of Respiratory Cell and Molecular Biology·Karina KrotovaMark L Brantly
Jan 14, 2020·BMC Musculoskeletal Disorders·Chang-Meen SungHyung Bin Park
Aug 9, 2020·Annals of the New York Academy of Sciences·L Cody SmithDebra L Laskin
Dec 5, 2018·Proceedings of the National Academy of Sciences of the United States of America·Sho ShibataHajime Karasuyama
Aug 2, 2015·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nathachit LimjunyawongWayne Mitzner
Apr 10, 2019·American Journal of Respiratory Cell and Molecular Biology·Shigen HayashiNobuyuki Hizawa
Feb 7, 2017·Cell and Tissue Research·John M CraigWayne Mitzner
Sep 21, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yu WangChunming Wang
Jun 4, 2021·Environmental Science and Pollution Research International·Farzaneh SohrabiSeyyed Ali Mard
Jun 19, 2019·Gerontology·Luis I Prieto, Darren J Baker

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis