A novel anti‐inflammatory role for secretory phospholipase A2 in immune complex‐mediated arthritis

Phospholipase A 2 (PLA 2 ) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA 2 enzymes (sPLA 2 ), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA 2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene‐deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA 2 isoform plays a novel anti‐inflammatory role that opposes the pro‐inflammatory activity of group IIA sPLA 2 . Mechanistically, group V sPLA 2 counter‐regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti‐inflammatory function for a PLA 2 and identify group V sPLA 2 as a potential biotherapeutic for treatment of immune‐complex‐mediated inflammation.