Proline-Glycine-Proline Peptides Are Critical in the Development of Smoke-Induced Emphysema

Chronic obstructive pulmonary disease (COPD) is a major cause of worldwide mortality and is characterized by an excessive airway neutrophilic response. The neutrophil chemoattractant proline-glycine-proline (PGP) and its more potent acetylated form (acPGP) have been found to be elevated in COPD patients and act via CXCR2. Here, we investigate the impact of neutralizing PGP peptides in a murine model for emphysema. The PGP neutralizing peptide L-arginine-threonine-arginine (RTR) was used first in a 6-week model of cigarette smoke exposure, where it attenuated lung inflammation. Further a chronic cigarette smoke exposure was conducted with mice starting RTR treatment after 10 weeks of smoke exposure and then continuing the treatment together with the smoke exposure during the last 13 weeks, totaling 23 weeks of smoke exposure. RTR significantly inhibited neutrophil and macrophage influx into the lungs in the 6-week model of exposure. RTR also attenuated the development of emphysema, normalized lung volumes,...