A single dose of lipopolysaccharide into mice with emphysema mimics human Chronic obstructive pulmonary disease exacerbation as assessed by micro-computed tomography

Satoshi Kobayashi, Reiko Fujinawa, Fumi Ota, Shiho Kobayashi, Takashi Angata, Manabu Ueno, Toshitaka Maeno, Shinobu Kitazume, Keiichi Yoshida, Takeo Ishii, Congxiao Gao, Kazuaki Ohtsubo, Yoshiki Yamaguchi, Tomoko Betsuyaku, Kozui Kida, Naoyuki Taniguchi

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Chronic obstructive pulmonary disease (COPD), manifested as emphysema and chronic airway obstruction, can be exacerbated by bacterial and viral infections. Although the frequency of exacerbations increases as the disease progresses, the mechanisms underlying this phenomen on a relargely unknown, and there is a need for a simple in vivo exacerbation model. In this study, we compared four groups of mice treated with PBS alone, elastase alone, LPS alone, and elastase plus LPS. A single intratracheal administration of LPS to mice with elastase-induced emphysema provoked infiltration of inflammatory cells, especiallyCD8+ T cells, in to alveolar spaces and increased matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and perforin production in bronchoalveolar lavage fluid at the acute inflammatory phase compared with the other groups. We also measured the percentage of low-attenuation area (LAA%) in the above mice using micro-computed X-ray tomography. The LAA% was the most sensitive parameter forquantitative assessments of emphysema among all the parameters evaluated. Using the parameter of LAA%, we found significantly more severe alveolar destruction in the group treated with elastase plus LPS compared with the other groups during longtermlongitudinalobservations.Webuiltthree-dimensionalimagesof the emphysema and confirmed that the lungs of elastase plus LPS-treated mice contained larger emphysematous areas than mice treated with elastase alone. Although human exacerbation of COPD is clinically and pathologically complicated, this simple mouse model mimics human cases to some extent and willbeuseful for elucidating its mechanism and developing therapeutic strategies.

Original languageEnglish
Pages (from-to)971-977
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume49
Issue number6
DOIs
Publication statusPublished - 2013 Dec 1

Keywords

  • Computed tomography
  • Elastase
  • Emphysema
  • Exacerbation
  • LPS

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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    Kobayashi, S., Fujinawa, R., Ota, F., Kobayashi, S., Angata, T., Ueno, M., Maeno, T., Kitazume, S., Yoshida, K., Ishii, T., Gao, C., Ohtsubo, K., Yamaguchi, Y., Betsuyaku, T., Kida, K., & Taniguchi, N. (2013). A single dose of lipopolysaccharide into mice with emphysema mimics human Chronic obstructive pulmonary disease exacerbation as assessed by micro-computed tomography. American journal of respiratory cell and molecular biology, 49(6), 971-977. https://doi.org/10.1165/rcmb.2013-0074OC