- Meeting abstract
- Open Access
Mechanisims of asthma and allergic disease – 1093. A novel human anti-VCAM-1 Monoclonal antibody Ameliorates airway inflammation and remodeling in murine asthma model
© Lee et al; licensee BioMed Central Ltd. 2013
- Published: 23 April 2013
- Airway Inflammation
- Vascular Cell Adhesion
- Allergic Inflammation
- Type 2helper
Asthma is a chronic inflammatory disease induced by Type 2helper T cells (Th2) and eosinophils. Vascular cell adhesion molecule-1(VCAM-1) is the regulatory receptor implicated with recruiting eosinophils andlymphocytes to pathologic site in asthma. A monoclonal antibody (mAb)against VCAM-1 may attenuate allergic inflammation and pathophysiologicfeatures of asthma. Weevaluated whether a recently developed human anti-VCAM-1mAb can inhibit pathophysiologic features of asthma in a murine asthma modelinduced by ovalbumin (OVA).
We evaluated whether human anti-VCAM-1 mAb binds to human ormouse VCAM-1. Leukocyte adhesion inhibition assay was performed toevaluate the in vitro blocking activity of human anti-VCAM-1 mAb. OVAsensitized BALB/c mice were treated with human anti-VCAM-1 mAb orisotype control Ab before intranasal OVA challenge. We evaluated airwayhyperresponsiveness (AHR) and cell counts in bronchoalveolar lavage (BAL)fluid, measured inflammatory cytokines, and examined histopathologicalfeatures, including VCAM-1 immunohistochemistry.
The human anti-VCAM-1 mAb bound to human and mouse VCAM-1molecules and inhibited adhesion of human leukocytes in vitro. AHR andinflammatory cell counts in BAL fluid were reduced in mice treated withhuman anti-VCAM-1 mAb as compared to a control Ab. The levels ofinterleukin (IL)-5 and IL-13, and transforming growth factor-β in lung tissuewere decreased in treated mice. Human anti-VCAM-1 mAb reduced goblet cellhyperplasia and peribronchial fibrosis. In vivo VCAM-1 expression decreasedin treated group.
Human anti-VCAM-1 mAb can attenuate allergic inflammationand pathophysiological features of asthma in OVA induced murine asthmamodel. This data suggested that human anti-VCAM-1 mAb could be an additionalanti-asthma therapeutic medicine.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.