The role of anti-elastin antibodies in a mouse model of asthma
Tomoshige Wakayama,1 Kumiya Sugiyama,1,2 Shingo Tokita,1 Hajime Arifuku,1 Naotatsu Otsuji,1 Kei Sugitate,1 Takayoshi Owada,1 Kenya Koyama,1 Hirokuni Hirata,1 Masafumi Arima,3 Yasutsugu Fukushima1
1 Department of Respiratory Medicine and Clinical Immunology Dokkyo Medical University, Saitama Medical Center, Saitama, Japan
2 National Hospital Organization, Utsunomiya National Hospital, Tochigi, Japan
3 Department of Rheumatology, Dokkyo Medical University, Tochigi, Japan
Abstract
Background: The role of anti-elastin antibody (Ab) in the lung is unclear, although they may be involved in chronic obstructive pulmonary disease (COPD). Recently, increased anti-elastin Ab levels were reported in asthma.
Objective: To elucidate the role of anti-elastin Ab in asthma, we created a murine asthma model. Anti-elastin Ab in the airway was neutralized by intratracheal administration of elastin peptide, and the inhibitory effects of anti-elastin Ab on airway remodeling were evaluated.
Methods: BALB/c mice were immunized with ovalbumin (OVA) on days 0 and 14. After immunization, the mice received booster OVA via inhalation twice per week for 9 weeks, and bronchoalveolar lavage fluid (BALF) and lung tissues were evaluated.
Results: In lung tissues, airway remodeling occurred after 9 weeks of OVA sensitization. Peak levels of anti-elastin Ab and eosinophils in BALF were detected after 3 weeks of OVA sensitization. Anti-elastin Ab and eosinophil levels in BALF were significantly reduced after 3 weeks by the neutralization of anti-elastin Ab. Peak transforming growth factor-β1 levels in BALF were detected at 3 weeks after OVA sensitization and were significantly reduced by the neutralization of anti-elastin Ab. Airway remodeling in lung tissues was also significantly inhibited by the neutralization of anti-elastin Ab.
Conclusion: In our murine asthma model, anti-elastin Ab was recruited to the airway by OVA-induced allergic inflammation. Airway remodeling was inhibited by the neutralization of anti-elastin Ab. Anti-elastin Ab may contribute to the progression of airway remodeling.
Key words: Anti-elastin antibodies, Airway remodeling, Asthma, Eosinophils, TGF-β