Specific physiological roles of cytosolic phospholipase A2 as defined by gene knockouts

Adam Sapirstein, Joseph V. Bonventre

Research output: Contribution to journalReview article

Abstract

The cytosolic 85 kDa phospholipase A2 (cPLA2) is a unique member of the phospholipase A2 (PLA2) superfamily. Because PLA2 activity and eicosanoid production are important in normal and pathophysiological states we and the laboratory of Shimizu created a mouse deficient in cPLA2 (cPLA2(-/-) mouse). cPLA2(-/-) mice develop normally but the females have severe reproductive defects. cPLA2(-/-) mice suffer smaller infarcts and fewer neurological deficits after transient occlusion of the middle cerebral artery and have less injury after administration of a dopaminergic selective neurotoxin. cPLA2(-/-) mice have a more rapid recovery from allergen-induced bronchoconstriction and have no airway hyperresponsiveness. Peritoneal macrophages from cPLA2(-/-) mice fail to produce prostaglandins, leukotriene B4 and cysteinyl leukotrienes after stimulation. Bone marrow-derived mast cells from cPLA2(-/-) mice fail to produce eicosanoids in either immediate or delayed phase responses. Thus the cPLA2 knockout mouse has revealed important roles of cPLA2 in normal fertility, generation of eicosanoids from inflammatory cells, brain injuries and allergic responses. Furthermore the cPLA2(-/-) mouse reveals that the many other forms of PLA2 cannot replace many functions of cPLA2. The importance of cPLA2 in inflammation and tissue injury suggests that pharmacological targeting of this enzyme may have important therapeutic benefits. (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1488
Issue number1-2
DOIs
StatePublished - Oct 31 2000
Externally publishedYes

Keywords

  • Allergy
  • Asthma
  • Cytosolic phospholipase A
  • Fertility
  • Macrophage
  • Stroke

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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