Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation

Kentaro Tamura, Koichiro Matsumoto, Satoru Fukuyama, Keiko Kano, Yumiko Ishii, Ken Tonai, Miyoko Tatsuta, Aimi Enokizu, Hiromasa Inoue, Yoichi Nakanishi

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2 Citations (Scopus)


Asthma and chronic obstructive pulmonary disease (COPD), chronic airway inflammatory diseases characterized by airflow limitation, have different etiologies and pathophysiologies. Asthma–COPD Overlap (ACO) has recently been used for patients with mixed asthma and COPD. The pathophysiological mechanisms of ACO have not been clearly understood due to the lack of an appropriate murine model. To investigate its pathophysiology, we examined a murine model by allergen challenge in surfactant protein-D (SP-D)-deficient mice that spontaneously developed pulmonary emphysema. SP-D-deficient mice were sensitized and challenged by ovalbumin (OVA). Lungs and bronchoalveolar lavage fluid (BALF) were collected for analysis, and static lung compliance and airway hyperresponsiveness (AHR) were measured 48 h after the last OVA challenge. In SP-D-deficient, naïve, or OVA-challenged mice, the mean linear intercept and static lung compliance were increased compared with wild-type (WT) mice. There was no significant difference in goblet cell hyperplasia and the gene expression of Mucin 5AC (MUC5AC) between SP-D-deficient and WT OVA-challenged mice. In SP-D-deficient OVA-challenged mice, airway hyperresponsiveness was significantly enhanced despite the lower eosinophil count and the concentration of interleukin (IL)-5 and IL-13 in BALF compared with WT OVA-challenged mice at 120 ventilations per minute. When mice were ventilated at a lower ventilation frequency of 100 ventilations per minute, elevated airway hyperresponsiveness in SP-D-deficient OVA-challenged mice was diminished. This model of emphysematous change with allergic airway inflammation raises the possibility that frequency-dependent airway hyperresponsiveness may be involved in the pathophysiology of ACO.

Original languageEnglish
Article numbere13568
JournalPhysiological Reports
Issue number2
Publication statusPublished - Jan 2018

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)


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