The neutrophil chemoattractant peptide proline-glycine-proline is associated with acute respiratory distress syndrome

ARDS is characterized by unrelenting PMN inflammation and vascular permeability. The matrikine proline-glycine-proline (PGP) and acetylated PGP (Ac-PGP) have been shown to induce PMN inflammation and endothelial permeability in vitro and in vivo. In this study, we investigated the presence and role of airway PGP peptides in acute lung injury (ALI)/ARDS. P. aeruginosa-derived LPS was instilled intratracheally (i.t) in mice to induce ALI and increased Ac-PGP with neutrophil inflammation was noted. The PGP inhibitory peptide, RTR (arginine-threonine-arginine), was administered (i.t.) 30 minutes before or 6 hours after LPS injection. Lung injury was evaluated by detecting neutrophil infiltration and permeability changes in the lung. Pre- and post-treatment with RTR significantly inhibited LPS-induced ALI by attenuating lung neutrophil infiltration, pulmonary permeability and parenchymal inflammation. To evaluate the role of PGP levels in ARDS, mini-bronchoalveolar lavage was collected from 9 ARDS, 4 cardiogen...