Importance of group X-secreted phospholipase A2 in allergen-induced airway inflammation and remodeling in a mouse asthma model

J Exp Med. 2007 Apr 16;204(4):865-77. doi: 10.1084/jem.20070029. Epub 2007 Apr 2.

Abstract

Arachidonic acid metabolites, the eicosanoids, are key mediators of allergen-induced airway inflammation and remodeling in asthma. The availability of free arachidonate in cells for subsequent eicosanoid biosynthesis is controlled by phospholipase A(2)s (PLA(2)s), most notably cytosolic PLA(2)-alpha. 10 secreted PLA(2)s (sPLA(2)s) have also been identified, but their function in eicosanoid generation is poorly understood. We investigated the role of group X sPLA(2) (sPLA(2)-X), the sPLA(2) with the highest in vitro cellular phospholipolysis activity, in acute and chronic mouse asthma models in vivo. The lungs of sPLA(2)-X(-/-) mice, compared with those of sPLA(2)-X(+/+) littermates, had significant reduction in ovalbumin-induced infiltration by CD4(+) and CD8(+) T cells and eosinophils, goblet cell metaplasia, smooth muscle cell layer thickening, subepithelial fibrosis, and levels of T helper type 2 cell cytokines and eicosanoids. These data direct attention to sPLA(2)-X as a novel therapeutic target for asthma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / immunology*
  • Animals
  • Asthma / enzymology*
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / pathology
  • Cytokines / metabolism
  • Disease Models, Animal*
  • Eicosanoids / metabolism
  • Gene Expression Regulation, Enzymologic
  • Group X Phospholipases A2
  • Inflammation / enzymology
  • Inflammation / genetics
  • Inflammation / immunology
  • Metaplasia / enzymology
  • Metaplasia / pathology
  • Mice
  • Mice, Knockout
  • Phospholipases A / deficiency
  • Phospholipases A / genetics
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Th2 Cells / enzymology

Substances

  • Allergens
  • Cytokines
  • Eicosanoids
  • Phospholipases A
  • Group X Phospholipases A2
  • Phospholipases A2
  • Pla2g10 protein, mouse