A novel human anti-VCAM-1 monoclonal antibody ameliorates airway inflammation and remodeling in murine asthma model
Other Titles
새로운 인간 항-VCAM-1 단클론 항체가 생쥐 천식 모델의 기도 염증과 개형에 미치는 영향
Authors
이재현
Issue Date
2012
Description
Dept. of Medicine/박사
Abstract
Background: Asthma is a chronic inflammatory disease induced by Type 2 helper T cells (Th2) and eosinophils. Vascular cell adhesion molecule-1 (VCAM-1) is the regulatory receptor implicated with recruiting eosinophils and lymphocytes to pathologic site in asthma. A monoclonal antibody (mAb) against VCAM-1 may attenuate allergic inflammation and pathophysiologic features of asthma.Objective: To evaluate whether a recently developed human anti-VCAM-1 mAb can inhibit pathophysiologic features of asthma in a murine asthma model induced by ovalbumin (OVA).Methods: We evaluated whether human anti-VCAM-1 mAb binds to human or mouse VCAM-1. Leukocyte adhesion inhibition assay was performed to evaluate the in vitro blocking activity of human anti-VCAM-1 mAb. OVA sensitized BALB/c mice were treated with human anti-VCAM-1 mAb or isotype control Ab before intranasal OVA challenge. We evaluated airway hyperresponsiveness (AHR) and cell counts in bronchoalveolar lavage (BAL) fluid, measured inflammatory cytokines, and examined histopathological features, including VCAM-1 immunohistochemistry.Results: The human anti-VCAM-1 mAb bound to human and mouse VCAM-1 molecules and inhibited adhesion of human leukocytes in vitro. AHR and inflammatory cell counts in BAL fluid were reduced in mice treated with human anti-VCAM-1 mAb as compared to a control Ab. The levels of interleukin (IL)-5 and IL-13, and transforming growth factor- in lung tissue were decreased in treated mice. Human anit-VCAM-1 mAb reduced goblet cell hyperplasia and peribronchial fibrosis. In vivo VCAM-1 expression decreased in treated group.Conclusion: Human anti-VCAM-1 mAb can attenuate allergic inflammation and pathophysiological features of asthma in OVA induced murine asthma model. This data suggest that human anti-VCAM-1 mAb could be an additional anti-asthma therapeutic medicine.