A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation

Academic Article

Abstract

  • Leukotriene A hydrolase (LTA H) is a proinflammatory enzyme that generates the inflammatory mediator leukotriene B (LTB ). LTA 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 H, which facilitated the resolution of inflammation. In contrast, cigarette smoke, a major risk factor for the development of COPD, selectively inhibited LTA H aminopeptidase activity, which led to the accumulation of PGP and neutrophils. These studies imply that therapeutic strategies inhibiting LTA H to prevent LTB generation may not reduce neutrophil recruitment because of elevated levels of PGP. 4 4 4 4 4 4 4 4 4
  • Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Author List

  • Snelgrove RJ; Jackson PL; Hardison MT; Noerager BD; Kinloch A; Gaggar A; Shastry S; Rowe SM; Shim YM; Hussell T
  • Start Page

  • 90
  • End Page

  • 94
  • Volume

  • 330
  • Issue

  • 6000