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A novel human anti-VCAM-1 monoclonal antibody ameliorates airway inflammation and remodelling

Authors
 Jae-Hyun Lee  ;  Jung-Ho Sohn  ;  Su Yeon Ryu  ;  Chein-Soo Hong  ;  Kyung D. Moon  ;  Jung-Won Park 
Citation
 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Vol.17(10) : 1271-1281, 2013 
Journal Title
 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 
ISSN
 1582-1838 
Issue Date
2013
MeSH
Animals ; Antibodies, Monoclonal/immunology* ; Asthma/immunology* ; Asthma/therapy ; Humans ; Mice ; Mice, Inbred BALB C ; Vascular Cell Adhesion Molecule-1/immunology*
Keywords
VCAM-1 ; allergic inflammation ; anti-inflammatory effect ; asthma ; cell adhesion molecule ; monoclonal antibody
Abstract
Asthma is a chronic inflammatory disease induced by Type 2 helper T cells and eosinophils. Vascular cell adhesion molecule-1 (VCAM-1) has been implicated in recruiting eosinophils and lymphocytes to pathological sites in asthma as a regulatory receptor. Accordingly, monoclonal antibody (mAb) against VCAM-1 may attenuate allergic inflammation and pathophysiological features of asthma. We attempted to evaluate whether a recently developed human anti-VCAM-1 mAb can inhibit the pathophysiological features of asthma in a murine asthma model induced by ovalbumin (OVA). Leucocyte 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 bronchoalveolar lavage fluid analysis, measured inflammatory cytokines and examined histopathological features. The human anti-VCAM-1 mAb bound to human and mouse VCAM-1 molecules and inhibited adhesion of human leucocytes in vitro. AHR and inflammatory cell counts in bronchoalveolar lavage fluid were reduced in mice treated with human anti-VCAM-1 mAb as compared with a control Ab. The levels of interleukin (IL)-5 and IL-13, as well as transforming growth factor-β, in lung tissue were decreased in treated mice. Human anti-VCAM-1 mAb reduced goblet cell hyperplasia and peribronchial fibrosis. In vivo VCAM-1 expression decreased in the treated group. In conclusion, human anti-VCAM-1 mAb attenuated allergic inflammation and the pathophysiological features of asthma in OVA-induced murine asthma model. The results suggested that human anti-VCAM-1 mAb could potentially be used as an additional anti-asthma therapeutic medicine.
Full Text
http://onlinelibrary.wiley.com/doi/10.1111/jcmm.12102/abstract
DOI
10.1111/jcmm.12102
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Jung Won(박중원) ORCID logo https://orcid.org/0000-0003-0249-8749
Sohn, Jung Ho(손정호)
Lee, Jae Hyun(이재현) ORCID logo https://orcid.org/0000-0002-0760-0071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/88656
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