Abstract
Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and 2) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.
| Original language | English (US) |
|---|---|
| Pages (from-to) | L757-L763 |
| Journal | American journal of physiology. Lung cellular and molecular physiology |
| Volume | 316 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2019 |
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Keywords
- animal model
- atopic
- eosinophils
- neutrophils
- pulmonary function
ASJC Scopus subject areas
- Physiology
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology
Cite this
Age-dependent pulmonary reactivity to house dust mite allergen : a model of adult-onset asthma? / Mack, Savannah; Shin, Jinho; Ahn, Yoomin; Castaneda, Alejandro R.; Peake, Janice; Fulgar, Ciara; Zhang, Jing Jing; Cho, Yoon Hee; Pinkerton, Kent E.
In: American journal of physiology. Lung cellular and molecular physiology, Vol. 316, No. 5, 01.05.2019, p. L757-L763.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Age-dependent pulmonary reactivity to house dust mite allergen
T2 - a model of adult-onset asthma?
AU - Mack, Savannah
AU - Shin, Jinho
AU - Ahn, Yoomin
AU - Castaneda, Alejandro R.
AU - Peake, Janice
AU - Fulgar, Ciara
AU - Zhang, Jing Jing
AU - Cho, Yoon Hee
AU - Pinkerton, Kent E
PY - 2019/5/1
Y1 - 2019/5/1
N2 - Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and 2) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.
AB - Asthma is a heterogeneous disease differentiated by factors like allergen sensitivity, inflammation, sex, and age at onset. The mouse model is widely used to study the early-life development of allergic asthma. However, age-dependent allergen responses later in life remain relatively understudied and lack a widely accepted model. To differentiate age-dependent responses to the ubiquitous house dust mite (HDM), 3- and 9-mo-old female C57BL/6 mice were randomized into two groups each and exposed to HDM or phosphate-buffered saline (control) via intranasal instillation for sensitization and challenge phases. At 24 h after challenge, all mice underwent pulmonary function testing and methacholine challenge. Bronchoalveolar lavage fluid (BALF) was collected for assessment of cell differentials, and right lung lobes were fixed, sectioned, and stained for histopathology and immunohistochemistry. Both age groups demonstrated strong inflammatory/allergic responses to HDM exposure. However, only 9-mo-old HDM-exposed mice demonstrated significant airway hyperresponsiveness compared with age-matched controls. These HDM-exposed mice also had 1) statistically significant increases in tissue bronchiolitis, perivasculitis, and BALF neutrophilia relative to their younger counterparts and 2) significantly increased extent of immunostaining compared with all other groups. This study presents a potential model for adult-onset asthma, focusing specifically on the atopic, perimenopausal female phenotype. Our findings suggest that lung function declines with age and that the inflammatory profile of this adult subgroup is a mixed, rather than a simple, atopic, Th2 response. This model may enhance our understanding of how age influences the development of asthmic-like symptoms in older subgroups.
KW - animal model
KW - atopic
KW - eosinophils
KW - neutrophils
KW - pulmonary function
UR - http://www.scopus.com/inward/record.url?scp=85065217065&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065217065&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00468.2018
DO - 10.1152/ajplung.00468.2018
M3 - Article
VL - 316
SP - L757-L763
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
SN - 1040-0605
IS - 5
ER -