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Advances in Pharmacological Sciences
Volume 2012, Article ID 768720, 16 pages
http://dx.doi.org/10.1155/2012/768720
Research Article

Allosteric Modulation of Beta1 Integrin Function Induces Lung Tissue Repair

1Avipero Ltd., 5th Floor, 125 Princes Street, Edinburgh EH2 4AD, UK
2School of Biomedical Sciences, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK
3Division of Pathology, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK
4MRC Centre for Inflammation Research, The Queen's Medical Research Institute, The University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK

Received 16 August 2011; Revised 21 October 2011; Accepted 31 October 2011

Academic Editor: Chi Hin Cho

Copyright © 2012 Rehab AlJamal-Naylor et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The cellular cytoskeleton, adhesion receptors, extracellular matrix composition, and their spatial distribution are together fundamental in a cell's balanced mechanical sensing of its environment. We show that, in lung injury, extracellular matrix-integrin interactions are altered and this leads to signalling alteration and mechanical missensing. The missensing, secondary to matrix alteration and cell surface receptor alterations, leads to increased cellular stiffness, injury, and death. We have identified a monoclonal antibody against β1 integrin which caused matrix remodelling and enhancement of cell survival. The antibody acts as an allosteric dual agonist/antagonist modulator of β1 integrin. Intriguingly, this antibody reversed both functional and structural tissue injury in an animal model of degenerative disease in lung.