title: A novel human anti-VCAM-1 monoclonal antibody ameliorates airway inflammation and remodelling.
abstract: 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.
authors.affiliation: Division of Allergy and Immunology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; Institute of Allergy, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Sohn
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Ryu
authors.forename: Chein-Soo
authors.initials: CS
authors.lastname: Hong
authors.forename: Kyung D
authors.initials: KD
authors.lastname: Moon
authors.forename: Jung-Won
authors.initials: JW
authors.lastname: Park
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D019010:Vascular Cell Adhesion Molecule-1 / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D019010:Vascular Cell Adhesion Molecule-1
keywords: VCAM-1; allergic inflammation; anti-inflammatory effect; asthma; cell adhesion molecule; monoclonal antibody