Group X secretory phospholipase A2 induces potent productions of various lipid mediators in mouse peritoneal macrophages

We have previously shown the expression of group X secretory phospholipase A₂ (sPLA₂-X) in mouse splenic macrophages and its powerful potency for releasing fatty acids from various intact cell membranes. Here, we examined the potency of sPLA₂-X in the production of lipid mediators in murine peritoneal macrophages. Mouse sPLA₂-X was found to induce a marked release of fatty acids including arachidonic acid and linoleic acid, which contrasted with little, if any, release by the action of group IB and IIA sPLA₂s. In resting macrophages, sPLA₂-X elicited a modest production of prostaglandin E₂ and thromboxane A₂. After the induction of cyclooxygenase-2 (COX-2) by pretreatment with lipopolysaccharide, a dramatic increase in the production of these eicosanoids was observed in sPLA₂-X-treated macrophages, which was completely blocked by the addition of either the specific sPLA₂ inhibitor indoxam or the COX inhibitor indomethacin. In accordance with its higher hydrolyzing activity toward phosphatidylcholine, mouse sPLA₂-X induced a potent production of lysophosphatidylcholine. These findings strongly suggest that sPLA₂-X plays a critical role in the production of various lipid mediators from macrophages. These events might be relevant to the progression of various pathological states, including chronic inflammation and atherosclerosis.