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Mechanisims of asthma and allergic disease – 1093. A novel human anti-VCAM-1 Monoclonal antibody Ameliorates airway inflammation and remodeling in murine asthma model
World Allergy Organization Journal volume 6, page P89 (2013)
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.
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Lee, JH., Sohn, JH., Ryu, S.Y. et al. Mechanisims of asthma and allergic disease – 1093. A novel human anti-VCAM-1 Monoclonal antibody Ameliorates airway inflammation and remodeling in murine asthma model. World Allergy Organ J 6, P89 (2013). https://doi.org/10.1186/1939-4551-6-S1-P89
- Airway Inflammation
- Vascular Cell Adhesion
- Allergic Inflammation
- Type 2helper