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

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

Research output: Contribution to journalArticle

Abstract

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
Volume6
Issue number2
DOIs
Publication statusPublished - Jan 2018

Fingerprint

Emphysema
Pulmonary Surfactant-Associated Protein D
Ovalbumin
Inflammation
Bronchoalveolar Lavage Fluid
Ventilation
Lung Compliance
Chronic Obstructive Pulmonary Disease
Mucin 5AC
Asthma
Pulmonary Emphysema
Goblet Cells
Interleukin-13
Interleukin-5
Eosinophils
Allergens
Hyperplasia
Gene Expression

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation. / Tamura, Kentaro; Matsumoto, Koichiro; Fukuyama, Satoru; Kan-o, Keiko; Ishii, Yumiko; Tonai, Ken; Tatsuta, Miyoko; Enokizu, Aimi; Inoue, Hiromasa; Nakanishi, Yoichi.

In: Physiological Reports, Vol. 6, No. 2, e13568, 01.2018.

Research output: Contribution to journalArticle

Tamura, K, Matsumoto, K, Fukuyama, S, Kan-o, K, Ishii, Y, Tonai, K, Tatsuta, M, Enokizu, A, Inoue, H & Nakanishi, Y 2018, 'Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation', Physiological Reports, vol. 6, no. 2, e13568. https://doi.org/10.14814/phy2.13568
Tamura, Kentaro ; Matsumoto, Koichiro ; Fukuyama, Satoru ; Kan-o, Keiko ; Ishii, Yumiko ; Tonai, Ken ; Tatsuta, Miyoko ; Enokizu, Aimi ; Inoue, Hiromasa ; Nakanishi, Yoichi. / Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation. In: Physiological Reports. 2018 ; Vol. 6, No. 2.
@article{8c31848b204d4426ad5e34fd099698fa,
title = "Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation",
abstract = "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, na{\"i}ve, 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.",
author = "Kentaro Tamura and Koichiro Matsumoto and Satoru Fukuyama and Keiko Kan-o and Yumiko Ishii and Ken Tonai and Miyoko Tatsuta and Aimi Enokizu and Hiromasa Inoue and Yoichi Nakanishi",
year = "2018",
month = "1",
doi = "10.14814/phy2.13568",
language = "English",
volume = "6",
journal = "Physiological Reports",
issn = "2051-817X",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Frequency-dependent airway hyperresponsiveness in a mouse model of emphysema and allergic inflammation

AU - Tamura, Kentaro

AU - Matsumoto, Koichiro

AU - Fukuyama, Satoru

AU - Kan-o, Keiko

AU - Ishii, Yumiko

AU - Tonai, Ken

AU - Tatsuta, Miyoko

AU - Enokizu, Aimi

AU - Inoue, Hiromasa

AU - Nakanishi, Yoichi

PY - 2018/1

Y1 - 2018/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85041237850&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041237850&partnerID=8YFLogxK

U2 - 10.14814/phy2.13568

DO - 10.14814/phy2.13568

M3 - Article

C2 - 29368450

AN - SCOPUS:85041237850

VL - 6

JO - Physiological Reports

JF - Physiological Reports

SN - 2051-817X

IS - 2

M1 - e13568

ER -