Volume 6 Supplement 1

2nd WAO International Scientific Conference (WISC 2012), Abstracts

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

  • Jae-Hyun Lee1,
  • Jung-Ho Sohn2,
  • Su Yeon Ryu3,
  • Kyung D Moon3,
  • Chein-Soo Hong1 and
  • Jung-Won Park1
World Allergy Organization Journal20136(Suppl 1):P89

DOI: 10.1186/1939-4551-6-S1-P89

Published: 23 April 2013

Background

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).

Methods

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.

Results

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.

Results

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.

Authors’ Affiliations

(1)
Div. of Allergy and Immunology, Dept. of Internal Medicine, Yonsei University College of Medicine
(2)
Department of Life Science, Research Institute for Natural Sciences, Hanyang University
(3)
Hanwha Chemical R&D Center

Copyright

© Lee et al; licensee BioMed Central Ltd. 2013

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.

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