Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2019 Dec 10;19(1):241.
doi: 10.1186/s12890-019-1001-9.

Comparison of asthma phenotypes in OVA-induced mice challenged via inhaled and intranasal routes

Dong Im Kim  1 , Mi-Kyung Song  1   2 , Kyuhong Lee  3   4
Affiliations
Comparative Study

Comparison of asthma phenotypes in OVA-induced mice challenged via inhaled and intranasal routes

Dong Im Kim et al. BMC Pulm Med. .

Abstract

Background: The respiratory system is exposed to various allergens via inhaled and intranasal routes. Murine models of allergic lung disease have been developed to clarify the mechanisms underlying inflammatory responses and evaluate the efficacy of novel therapeutics. However, there have been no comparative studies on differences in allergic phenotypes following inhaled vs. intranasal allergen challenge. In this study, we compared the asthmatic features of mice challenged via different routes following allergen sensitization and investigated the underlying mechanisms.

Methods: To establish ovalbumin (OVA)-induced allergic asthma models, BALB/c mice were sensitized to 20 μg OVA with 1 mg aluminum hydroxide by the intraperitoneal route and then challenged by inhalation or intranasal administration with 5% OVA for 3 consecutive days. Cellular changes and immunoglobulin (Ig) E levels in bronchoalveolar lavage fluid (BALF) and serum, respectively, were assessed. Histological changes in the lungs were examined by hematoxylin and eosin (H&E) and periodic acid Schiff (PAS) staining. Levels of T helper (Th)2 cytokines including interleukin (IL)-4, -5, and -13 in BALF and epithelial cytokines including IL-25 and -33 in BALF and lung tissues were measured by enzyme-linked immunosorbent assay and western blotting. Airway hyperresponsiveness (AHR) was evaluated by assessing airway resistance (Rrs) and elastance (E) via an invasive method.

Results: OVA-sensitized and challenged mice showed typical asthma features such as airway inflammation, elevated IgE level, and AHR regardless of the challenge route. However, H&E staining showed that inflammation of pulmonary vessels, alveolar ducts, and alveoli were enhanced by inhaled as compared to intranasal OVA challenge. PAS staining showed that intranasal OVA challenge induced severe mucus production accompanied by inflammation in bronchial regions. In addition, Th2 cytokine levels in BALF and AHR in lung were increased to a greater extent by inhalation than by intranasal administration of OVA. Epithelial cytokine expression, especially IL-25, was increased in the lungs of mice in the inhaled OVA challenge group.

Conclusion: OVA-sensitized mice exhibit different pathophysiological patterns of asthma including expression of epithelial cell-derived cytokines depending on the OVA challenge route. Thus, some heterogeneous phenotypes of human asthma can be replicated by varying the mode of delivery after OVA sensitization.

Keywords: Allergic asthma; Animal model; Asthma phenotypes; Challenge routes; Ovalbumin sensitization.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Changes in body weight of control and OVA-sensitized and challenged mice
Fig. 2
Fig. 2
Changes in relative lung and spleen weights of control and OVA-sensitized and challenged mice. a, b Relative lung (a) and spleen (b) weights were calculated using the following formula: relative organ weight = organ weight (g)/terminal body weight (g) × 100%. Bars represent the mean ± SD from five mice per group. #p < 0.05 vs. inhaled saline, *p < 0.05 vs. intranasal saline
Fig. 3
Fig. 3
Cellular changes in BALF. BALF cells were collected and analyzed 48 h after the last OVA challenge. Percentages of differential cells in BALF from control and OVA-sensitized and challenged mice (a). Total and differential cells in BALF (b). Bars represent the mean ± SD from five mice per group. #p < 0.05 vs. inhaled saline, *p < 0.05 vs. intranasal saline
Fig. 4
Fig. 4
Serum IgE levels in control and OVA-sensitized and challenged mice. Serum samples from all groups were collected 48 h after the last OVA challenge. Bars represent the mean ± SD from five mice per group. #p < 0.05 vs. inhaled saline, *p < 0.05 vs. intranasal saline
Fig. 5
Fig. 5
Infiltration of inflammatory cells and mucus secretion in lung tissue from control and OVA-sensitized and challenged mice. Representative H&E- and PAS-stained sections of lung and higher magnifications (a). Histological scoring of inflammatory cell infiltration (b) and goblet cells (c). Number of PAS+ cells were counted and normalized by area of basement membrane (d). Representative H&E- and PAS-stained sections in bronchi and bronchiole (e). Black and red arrows indicate inflammatory cells and goblet cells. B; bronchi, BL; bronchiole, A; alveolar, PV; perivascular. Bars represent the mean ± SD from five mice per group. #p < 0.05 vs. naïve control
Fig. 6
Fig. 6
Th2 cytokine levels in BALF. Enzyme immunoassay of IL-4 (a), IL-5 (b), and IL-13 (c) levels. Bars represent mean ± SD (n = 5/group). #p < 0.05 vs. inhaled saline, *p < 0.05 vs. intranasal saline
Fig. 7
Fig. 7
Changes in airway responsiveness according to methacholine concentration in control and OVA-sensitized and challenged mice. a Respiratory system resistance (Rrs) and (b) elastance (E) was measured 24 h after the last OVA challenge in mice. Bars represent the mean ± SEM (n = 5/group). #p < 0.05 vs. inhaled saline, *p < 0.05 vs. intranasal saline
Fig. 8
Fig. 8
Epithelial cytokine levels in BALF and lung tissues. Enzyme immunoassay of IL-25 (a) and IL-33 (b) levels. Relative density (c, d) and representative western blots (e) of IL-25 and IL-33 proteins in control and OVA-sensitized and challenged mice. Bars represent the mean ± SD (n = 5/group). #p < 0.05 vs. inhaled saline, *p < 0.05 vs. intranasal saline
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bousquet J, Jeffery PK, Busse WW, Johnson M, Vignola AM. Asthma: from bronchoconstriction to airways inflammation and remodeling. Am J Respir Crit Care Med. 2000;161:1720–1745. doi: 10.1164/ajrccm.161.5.9903102. - DOI - PubMed
    1. Fish JE, Peters SP. Airway remodeling and persistent airways obstruction in asthma. J Allergy Clin Immunol. 1999;104:509–516. doi: 10.1016/S0091-6749(99)70315-5. - DOI - PubMed
    1. Nials AT, Uddin S. Mouse models of allergic asthma: acute and chronic allergen challenge. Dis Model Mech. 2008;1:213–220. doi: 10.1242/dmm.000323. - DOI - PMC - PubMed
    1. Yáñez A, Cho SH, Soriano JB, Rosenwasser LJ, Rodrigo GJ, Rabe KF, et al. Asthma in the elderly: what we know and what we have yet to know. World Allergy Organ J. 2014;7:8. doi: 10.1186/1939-4551-7-8. - DOI - PMC - PubMed
    1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention (updated 2016). GINA; 2016. Available from: https://ginasthma.org/wp-content/uploads/2016/04/GINA-2016-main-report_t.... Accessed 5 Oct 2017.

Publication types

MeSH terms

-