Role of cytosolic phospholipase A2 in allergic response and parturition

Nature. 1997 Dec 11;390(6660):618-22. doi: 10.1038/37622.


Phospholipase A2 (PLA2) comprises a superfamily of enzymes that hydrolyse the ester bond of phospholipids at the sn-2 position. Among the members of this superfamily, cytosolic PLA2 has attracted attention because it preferentially hydrolyses arachidonoyl phospholipids and is activated by submicromolar concentrations of Ca2+ ions and by phosphorylation by mitogen-activated protein kinases (MAP kinases). Here we investigate the function of cytosolic PLA2 in vivo by using homologous recombination to generate mice deficient in this enzyme. These mice showed a marked decrease in their production of eicosanoids and platelet-activating factor in peritoneal macrophages. Their ovalbumin-induced anaphylactic responses were significantly reduced, as was their bronchial reactivity to methacholine. Female mutant mice failed to deliver offspring, but these could be rescued by administration of a progesterone-receptor antagonist to the mother at term. Considered together with previous findings, our results indicate that cytosolic PLA2 plays a non-redundant role in allergic responses and reproductive physiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphylaxis / enzymology
  • Animals
  • Bronchial Hyperreactivity / enzymology
  • Chimera
  • Cloning, Molecular
  • Cytosol / enzymology
  • Eicosanoids / biosynthesis
  • Female
  • Gene Targeting
  • Hypersensitivity / enzymology*
  • Labor, Obstetric*
  • Macrophages, Peritoneal / metabolism
  • Male
  • Methacholine Chloride
  • Mice
  • Mice, Inbred C57BL
  • Phospholipases A / deficiency
  • Phospholipases A / genetics
  • Phospholipases A / metabolism*
  • Phospholipases A2
  • Platelet Activating Factor / biosynthesis
  • Pregnancy


  • Eicosanoids
  • Platelet Activating Factor
  • Methacholine Chloride
  • Phospholipases A
  • Phospholipases A2