The cytosolic 85 kDa phospholipase A 2 (cPLA 2 ) is a unique member of the phospholipase A 2 (PLA 2 ) superfamily. Because PLA 2 activity and eicosanoid production are important in normal and pathophysiological states we and the laboratory of Shimizu created a mouse deficient in cPLA 2 (cPLA 2 −/− mouse). cPLA 2 −/− mice develop normally but the females have severe reproductive defects. cPLA 2 −/− 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. cPLA 2 −/− mice have a more rapid recovery from allergen-induced bronchoconstriction and have no airway hyperresponsiveness. Peritoneal macrophages from cPLA 2 −/− mice fail to produce prostaglandins, leukotriene B 4 and cysteinyl leukotrienes after stimulation. Bone marrow-derived mast cells from cPLA 2 −/− mice fail to produce eicosanoids in either immediate or delayed phase responses. Thus the cPLA 2 knockout mouse has revealed important roles of cPLA 2 in normal fertility, generation of eicosanoids from inflammatory cells, brain injuries and allergic responses. Furthermore the cPLA 2 −/− mouse reveals that the many other forms of PLA 2 cannot replace many functions of cPLA 2 . The importance of cPLA 2 in inflammation and tissue injury suggests that pharmacological targeting of this enzyme may have important therapeutic benefits.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids – Elsevier
Published: Oct 31, 2000
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