• Am. J. Physiol. Lung Cell Mol. Physiol. · Jan 2016

    Induction and regulation of murine emphysema by elastin peptides.

    • Mehdi Sellami, Aïda Meghraoui-Kheddar, Christine Terryn, Caroline Fichel, Nicole Bouland, Marie-Daniele Diebold, Moncef Guenounou, Stéphanie Héry-Huynh, and Richard Le Naour.
    • EA4683, SFR CAP-Santé, Université de Reims Champagne-Ardenne, Reims, France;
    • Am. J. Physiol. Lung Cell Mol. Physiol. 2016 Jan 1; 310 (1): L8-23.

    AbstractEmphysema is the major component of chronic obstructive pulmonary disease (COPD). During emphysema, elastin breakdown in the lung tissue originates from the release of large amounts of elastase by inflammatory cells. Elevated levels of elastin-derived peptides (EP) reflect massive pulmonary elastin breakdown in COPD patients. Only the EP containing the GXXPG conformational motif with a type VIII β-turn are elastin receptor ligands inducing biological activities. In addition, the COOH-terminal glycine residue of the GXXPG motif seems a prerequisite to the biological activity. In this study, we endotracheally instilled C57BL/6J mice with GXXPG EP and/or COOH-terminal glycine deleted-EP whose sequences were designed by molecular dynamics and docking simulations. We investigated their effect on all criteria associated with the progression of murine emphysema. Bronchoalveolar lavages were recovered to analyze cell profiles by flow cytometry and lungs were prepared to allow morphological and histological analysis by immunostaining and confocal microscopy. We observed that exposure of mice to EP elicited hallmark features of emphysema with inflammatory cell accumulation associated with increased matrix metalloproteinases and desmosine expression and of remodeling of parenchymal tissue. We also identified an inactive COOH-terminal glycine deleted-EP that retains its binding-activity to EBP and that is able to inhibit the in vitro and in vivo activities of emphysema-inducing EP. This study demonstrates that EP are key actors in the development of emphysema and that they represent pharmacological targets for an alternative treatment of emphysema based on the identification of EP analogous antagonists by molecular modeling studies.Copyright © 2016 the American Physiological Society.

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