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

Abstract

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 lipopolysaccharidetreated 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.

Interfacial Kinetic and Binding Properties of the Complete Set of Human and Mouse Groups I, II, V, X, and XII Secreted Phospholipases A2

“…6), yet efficient arachidonate liberation is seen when these cells are transfected with hGV and hGX cDNA (83). The amount of arachidonate produced by HEK293 cells forcibly overexpressing hGIIF (19) is more than would be expect from the data with exogenously added enzyme (Fig. 6).…”

“…One or more keratinocyte sPLA 2 is involved in the generation of free fatty acids, which are one of the main constituents of the permeability barrier of the outermost layer of skin (stratum corneum) (15,16). Physiological functions for groups IIC, IID, IIE, IIF, III, and XII sPLA 2 s have not yet been reported, although overexpression of groups IID, IIE, and IIF in HEK293 cells results in arachidonic acid release, which can be converted into prostaglandins (17)(18)(19). It is also clear that mammals contain a collection of proteins that bind sPLA 2 s tightly.…”

Group VIB Ca2+-independent Phospholipase A2γ Promotes Cellular Membrane Hydrolysis and Prostaglandin Production in a Manner Distinct from Other Intracellular Phospholipases A2

“…Interestingly, we found that iPLA 2 ␥-released AA is preferentially supplied to COX-1 for PGE 2 synthesis, an event that is in marked contrast with the fact that cPLA 2 and secretory PLA 2 enzymes display apparent COX-2 preference (12,43,(53)(54)(55)(56). Indeed, coexpression of iPLA 2 ␥ with either COX isoform in HEK293 cells revealed that COX-1-dependent PGE 2 production occurred preferentially in A23187-induced immediate and even IL-1/FCS-dependent delayed responses (Fig.…”

“…Nevertheless, our previous studies using this system have shown that cPLA 2 ␣ (12, 43), several secretory PLA 2 enzymes (43,(53)(54)(55)(56), and cPLA 2 ␥ (41) can elicit stimulus-coupled AA release, which is linked to PGE 2 production via both COX-1 and COX-2 in the immediate response and via COX-2 in the delayed response, observations that have been supported by other investigators using distinct experimental approaches (51,52,(57)(58)(59)(60)(61). In contrast, in HEK293 cells, iPLA 2 ␤ promotes stimulus-independent (basal), fatty acid-nonselective release that is poorly (if at all) coupled with COX-dependent PG synthesis (12,43), which may be a reflection of its membrane remodeling function.…”

Targeting lipid metabolism by the lipoprotein lipase inhibitor orlistat results in apoptosis of B-cell chronic lymphocytic leukemia cells

“…PLA2 g (PLA2G4C), group IIF phospholipase (PLA2G2F) and group IIE phospholipase (PLA2G2E) induce the release of arachidonate from phospholipids. [15][16][17] LEP14 and LEP13 18 were predicted in silico to have PLA2 activity, and PATE bears a putative PLA2 motif. 19 Adiponutrin is similar to patatin-like phospholipase domain-containing protein 3 and also shows PLA2 activity.…”