A Critical Role for LTA 4 H in Limiting Chronic Pulmonary Neutrophilic Inflammation

Abstract

Smoke Gets in Your Lungs Chronic obstructive pulmonary disease (COPD) is a leading cause of death in the United States, primarily caused by cigarette smoking. The chronic inflammation that leads to tissue damage and organ dysfunction in COPD is mediated in large part by neutrophils, a type of granulocytic immune cell. Snelgrove et al. (p. 90 , published online 2 September; see the Perspective by Barnes ) now provide an explanation for why neutrophils stick around in the lung during COPD. The neutrophil chemoattractant Pro-Gly-Pro (PGP) is a biomarker for COPD and promotes neutrophil accumulation. The enzyme leukotriene A 4 hydrolase degrades PGP in mice, and its activity was reduced by cigarette smoke both in vivo and in vitro. In contrast, during acute influenza infection in mice, leukotriene A 4 hydrolase functioned normally, allowing for PGP degradation and the resolution of inflammation. Thus, in COPD, cigarette smoking may lead to the accumulation PGP—which, in turn, could keep neutrophils in the lung to drive inflammation and subsequent lung damage and dysfunction.