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Cellular Arachidonate-releasing Function and Inflammation-associated Expression of Group IIF Secretory Phospholipase A2

2002; Elsevier BV; Volume: 277; Issue: 21 Linguagem: Inglês

10.1074/jbc.m112385200

1083-351X

Makoto Murakami, Kumiko Yoshihara, Satoko Shimbara, Gérard Lambeau, Michael H. Gelb, Alan G. Singer, Masatsugu Sawada, Naoki Inagaki, Hiroichi Nagai, Motoko Ishihara, Yukio Ishikawa, Toshiharu Ishii, Ichiro Kudo,

Cell Adhesion Molecules Research

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.