Various Secretory Phospholipase A(2) Enzymes Are Expressed In Rheumatoid Arthritis And Augment Prostaglandin Production In Cultured Synovial Cells

Although group IIA secretory phospholipase A(2) (sPLA(2)-IIA) is known to be abundantly present in the joints of patients with rheumatoid arthritis (RA), expression of other sPLA(2)S in this disease has remained unknown. In this study, we examined the expression and localization of six sPLA(2)S (groups IIA, IID, IIE, IIF, V and X) in human RA. Immunohistochemistry of RA sections revealed that sPLA(2)-IIA was generally located in synovial lining and sublining cells and cartilage chondrocytes, sPLA(2)-IID in lymph follicles and capillary endothelium, sPLA(2)-IIE in vascular smooth muscle cells, and sPLA(2)-V in interstitial fibroblasts. Expression levels of these group II subfamily sPLA(2)s appeared to be higher in severe RA than in inactive RA. sPLA(2)-X was detected in synovial lining cells and interstitial fibers in both active and inactive RA sections. Expression of sPLA(2)-IIF was partially positive, yet its correlation with disease states was unclear. Expression of sPLA(2) transcripts was also evident in cultured normal human synoviocytes, in which sPLA(2)-IIA and -V were induced by interleukin-1 and sPLA(2)-X was expressed constitutively. Adenovirus-mediated expression of sPLA(2)S in cultured synoviocytes resulted in increased prostaglandin E-2 production at low ng.mL(-1) concentrations. Thus, multiple sPLA(2)s are expressed in human RA, in which they may play a role in the augmentation of arachidonate metabolism or exhibit other cell type-specific functions.