Role of cytosolic phospholipase A2 in allergic response and parturition.
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.
Uozumi
N
N
Department of Biochemistry, University of Tokyo, Japan.
Kume
K
K
Nagase
T
T
Nakatani
N
N
Ishii
S
S
Tashiro
F
F
Komagata
Y
Y
Maki
K
K
Ikuta
K
K
Ouchi
Y
Y
Miyazaki
J
J
Shimizu
T
T
D000707:Anaphylaxis / Q000201:enzymology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000201:enzymology; D002678:Chimera; D003001:Cloning, Molecular; D003600:Cytosol / Q000201:enzymology; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D018390:Gene Targeting; D006967:Hypersensitivity / Q000201:enzymology*; D007743:Labor, Obstetric; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D016210:Methacholine Chloride; D051379:Mice; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000096:biosynthesis; D011247:Pregnancy
D015777:Eicosanoids; D010972:Platelet Activating Factor; D016210:Methacholine Chloride; D010741:Phospholipases A; D054467:Phospholipases A2