A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation.
Science
; 330(6000): 90-4, 2010 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-20813919
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligopeptides
/
Pneumonia
/
Smoke
/
Proline
/
Epoxide Hydrolases
/
Lung
/
Neutrophils
Type of study:
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
Science
Year:
2010
Document type:
Article
Affiliation country:
United States