Editors' ChoiceLung Disease

Smoke Gets in Your Lungs

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Sci. Signal.  05 Oct 2010:
Vol. 3, Issue 142, pp. ec309
DOI: 10.1126/scisignal.3142ec309

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. (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 A4 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 A4 hydrolase functioned normally, allowing for PGP degradation and the resolution of inflammation. Thus, in COPD, cigarette smoking may lead to the accumulation of PGP—which, in turn, could keep neutrophils in the lung to drive inflammation and subsequent lung damage and dysfunction.

R. J. Snelgrove, P. L. Jackson, M. T. Hardison, B. D. Noerager, A. Kinloch, A. Gaggar, S. Shastry, S. M. Rowe, Y. M. Shim, T. Hussell, J. E. Blalock, A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation. Science 330, 90–94 (2010). [Abstract] [Full Text]

P. J. Barnes, Neutrophils find smoke attractive. Science 330, 40–41 (2010). [Abstract] [Full Text]