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  • 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

  • 1,
  • 2,
  • 3,
  • 3,
  • 1 and
  • 1
World Allergy Organization Journal20136:373

https://doi.org/10.1186/1939-4551-6-S1-P89

  • Published:

Keywords

  • Asthma
  • Airway Inflammation
  • Vascular Cell Adhesion
  • Allergic Inflammation
  • Type 2helper

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, Seoul, South Korea
(2)
Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea
(3)
Hanwha Chemical R&D Center, Daejeon, South Korea

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