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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-03-10

AUTHORS

Manabu Ueno, Toshitaka Maeno, Satoshi Nishimura, Fusa Ogata, Hiroaki Masubuchi, Kenichiro Hara, Kouichi Yamaguchi, Fumiaki Aoki, Tatsuo Suga, Ryozo Nagai, Masahiko 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+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. More... »

PAGES

6332

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms7332

DOI

http://dx.doi.org/10.1038/ncomms7332

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1004003940

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25757189


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49 bisphosphonate alendronate
50 bisphosphonates
51 blunt
52 bone disease
53 bronchoalveolar fluid
54 caspase-3
55 crucial role
56 cytometric analysis
57 delivery
58 disease
59 effective treatment
60 elastase instillation
61 emphysema
62 enlargement
63 factor-κB signaling
64 fluid
65 induction
66 induction of apoptosis
67 inflammatory macrophages
68 inflammatory response
69 inhalation
70 inhibits
71 instillation
72 macrophages
73 mevalonate-dependent pathway
74 mice
75 nuclear factor-κB signaling
76 pathogenesis
77 pathogenesis of emphysema
78 pathway
79 phagocytotic activity
80 population
81 potential
82 pulmonary emphysema
83 resident alveolar macrophages
84 response
85 role
86 signaling
87 strategies
88 substantial amount
89 therapeutic potential
90 treatment
91 treatment of emphysema
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