The Neutrophil Chemoattractant Peptide Proline-Glycine-Proline Is Associated With Acute Respiratory Distress Syndrome (ARDS).

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 cardiogenic edema and 5 non- lung disease ventilated patients. PGP and myeloperoxidase (MPO) levels were measured and correlated with APACHE score, Pao2 to Fio2 (PF) and ventilator days. PGP and MPO levels in subjects with ARDS were significantly higher than cardiogenic edema and non- lung disease ventilated patients. Preliminary examination in both ARDS and non-ARDS populations demonstrated PGP levels significantly correlated with PF ratio, APACHE score and duration on ventilator. These results demonstrate an increase burden of PGP peptides in ARDS and suggest the need for future studies in ARDS cohorts to examine correlation with key clinical parameters.