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 A2 (sPLA2-IIF), a sPLA2enzyme uniquely containing a longer C-terminal extension. sPLA2-IIF increased spontaneous and stimulus-dependent release of AA, which was supplied to downstream cyclooxygenases and 5-lipoxygenase for eicosanoid production. sPLA2-IIF also enhanced interleukin 1-stimulated expression of cyclooxygenase-2 and microsomal prostaglandin E synthase. AA release by sPLA2-IIF was facilitated by oxidative modification of cellular membranes. Cellular actions of sPLA2-IIF occurred independently of the heparan sulfate proteoglycan glypican, which acts as a functional adaptor for other group II subfamily sPLA2s. Confocal microscopy revealed the location of sPLA2-IIF on the plasma membrane. The unique C-terminal extension was crucial for its plasma membrane localization and optimal cellular functions. sPLA2-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, sPLA2-IIF was detected in synovial lining cells, capillary endothelial cells, and plasma cells. These results suggest that sPLA2-IIF is a potent regulator of AA metabolism and participates in the inflammatory process under certain conditions.