These authors contributed equally to this study.
A novel human anti-VCAM-1 monoclonal antibody ameliorates airway inflammation and remodelling
Article first published online: 16 JUL 2013
© 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 17, Issue 10, pages 1271–1281, October 2013
How to Cite
Lee, J.-H., Sohn, J.-H., Ryu, S. Y., Hong, C.-S., Moon, K. D. and Park, J.-W. (2013), A novel human anti-VCAM-1 monoclonal antibody ameliorates airway inflammation and remodelling. Journal of Cellular and Molecular Medicine, 17: 1271–1281. doi: 10.1111/jcmm.12102
- Issue published online: 26 NOV 2013
- Article first published online: 16 JUL 2013
- Manuscript Accepted: 7 JUN 2013
- Manuscript Revised: 5 JUN 2013
- Manuscript Received: 5 DEC 2012
- monoclonal antibody;
- allergic inflammation;
- cell adhesion molecule;
- anti-inflammatory effect
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.