Arachidonate release and eicosanoid generation by group IIE phospholipase A(2).
The heparin-binding group II subfamily of secretory phospholipase A(2)s (sPLA(2)s), such as sPLA(2)-IIA and -IID, augments stimulus-induced arachidonic acid (AA) release through the cellular heparan sulfate proteoglycan (HSPG)-dependent pathway when transfected into HEK293 cells. Here we show that the closest homolog, sPLA(2)-IIE, also promotes stimulus-induced AA release and prostaglandin (PG) production similar to those elicited by HSPG-dependent sPLA(2)s. Confocal laser microscopic analysis demonstrates the location of sPLA(2)-IIE in cytoplasmic punctate compartments. sPLA(2)-IIE also enhances leukotriene (LT) production and granule exocytosis by RBL-2H3 mastocytoma cells. Expression of sPLA(2)-IIE was highly upregulated in mice injected with lipopolysaccharide (LPS) and in mice with experimental atopic dermatitis. These observations suggest that this enzyme plays a role in the inflammatory process, as proposed for other group II subfamily sPLA(2)s.
Murakami
Makoto
M
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. mako@pharm.showa-u.ac.jp
Yoshihara
Kumiko
K
Shimbara
Satoko
S
Lambeau
Gerard
G
Singer
Alan
A
Gelb
Michael H
MH
Sawada
Masatsugu
M
Inagaki
Naoki
N
Nagai
Hiroichi
H
Kudo
Ichiro
I
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D002460:Cell Line; D015777:Eicosanoids / Q000378:metabolism*; D005786:Gene Expression Regulation; D054501:Group II Phospholipases A2; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D007527:Isoenzymes / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding
D000925:Anticoagulants; D015777:Eicosanoids; D007527:Isoenzymes; D016718:Arachidonic Acid; D006493:Heparin; D010741:Phospholipases A; D054501:Group II Phospholipases A2