Cellular arachidonate-releasing function and inflammation-associated expression of group IIF secretory phospholipase A2.
Here we report the cellular arachidonate (AA)-releasing function of group IIF secretory phospholipase A(2) (sPLA(2)-IIF), a sPLA(2) enzyme uniquely containing a longer C-terminal extension. sPLA(2)-IIF increased spontaneous and stimulus-dependent release of AA, which was supplied to downstream cyclooxygenases and 5-lipoxygenase for eicosanoid production. sPLA(2)-IIF also enhanced interleukin 1-stimulated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase. AA release by sPLA(2)-IIF was facilitated by oxidative modification of cellular membranes. Cellular actions of sPLA(2)-IIF occurred independently of the heparan sulfate proteoglycan glypican, which acts as a functional adaptor for other group II subfamily sPLA(2)s. Confocal microscopy revealed the location of sPLA(2)-IIF on the plasma membrane. The unique C-terminal extension was crucial for its plasma membrane localization and optimal cellular functions. sPLA(2)-IIF expression was increased in various tissues from lipopolysaccharide-treated mice and in ears of mice with experimental atopic dermatitis. In human rheumatoid arthritic joints, sPLA(2)-IIF was detected in synovial lining cells, capillary endothelial cells, and plasma cells. These results suggest that sPLA(2)-IIF is a potent regulator of AA metabolism and participates in the inflammatory process under certain conditions.
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
Gerald
G
Gelb
Michael H
MH
Singer
Alan G
AG
Sawada
Masatsugu
M
Inagaki
Naoki
N
Nagai
Hiroichi
H
Ishihara
Motoko
M
Ishikawa
Yukio
Y
Ishii
Toshiharu
T
Kudo
Ichiro
I
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016718:Arachidonic Acid; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone