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A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation.


ABSTRACT: Leukotriene A(4) hydrolase (LTA(4)H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene B(4) (LTB(4)). LTA(4)H also possesses aminopeptidase activity with unknown substrate and physiological importance; we identified the neutrophil chemoattractant proline-glycine-proline (PGP) as this physiological substrate. PGP is a biomarker for chronic obstructive pulmonary disease (COPD) and is implicated in neutrophil persistence in the lung. In acute neutrophil-driven inflammation, PGP was degraded by LTA(4)H, which facilitated the resolution of inflammation. In contrast, cigarette smoke, a major risk factor for the development of COPD, selectively inhibited LTA(4)H aminopeptidase activity, which led to the accumulation of PGP and neutrophils. These studies imply that therapeutic strategies inhibiting LTA(4)H to prevent LTB(4) generation may not reduce neutrophil recruitment because of elevated levels of PGP.

SUBMITTER: Snelgrove RJ 

PROVIDER: S-EPMC3072752 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation.

Snelgrove Robert J RJ   Jackson Patricia L PL   Hardison Matthew T MT   Noerager Brett D BD   Kinloch Andrew A   Gaggar Amit A   Shastry Suresh S   Rowe Steven M SM   Shim Yun M YM   Hussell Tracy T   Blalock J Edwin JE  

Science (New York, N.Y.) 20100902 6000


Leukotriene A(4) hydrolase (LTA(4)H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene B(4) (LTB(4)). LTA(4)H also possesses aminopeptidase activity with unknown substrate and physiological importance; we identified the neutrophil chemoattractant proline-glycine-proline (PGP) as this physiological substrate. PGP is a biomarker for chronic obstructive pulmonary disease (COPD) and is implicated in neutrophil persistence in the lung. In acute neutrophil-driven inflamm  ...[more]

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