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.