Group X secretory phospholipase A(2) induces potent productions of variouslipid mediators in mouse peritoneal macrophages

We have previously shown the expression of group X secretory phospholipase A(2) (sPLA(2)-X) in mouse splenic macrophages and its powerful potency for releasing fatty acids from various intact cell membranes. Here, we examined the potency of sPLA(2)-X in the production of lipid mediators in murine pe ritoneal macrophages. Mouse sPLA(2)-X was found to induce a marked release of fatty acids including arachidonic acid and linoleic acid, which contrast ed with little, if any, release by the action of group IB and IIA sPLA(2)s. In resting macrophages, sPLA(2)-X elicited a modest production of prostagl andin E-2 and thromboxane A(2). After the induction of cyclooxygenase-2 (CO X-2) by pretreatment with lipopolysaccharide, a dramatic increase in the pr oduction of these eicosanoids was observed in sPLA(2)-X-treated macrophages , which was completely blocked by the addition of either the specific sPLA( 2) inhibitor indoxam or the COX inhibitor indomethacin. In accordance with its higher hydrolyzing activity toward phosphatidylcholine, mouse sPLA(2)-X induced a potent production of lysophosphatidylcholine. These findings str ongly suggest that sPLA(2)-X plays a critical role in the production of var ious lipid mediators from macrophages. These events might be relevant to th e progression of various pathological states, including chronic inflammatio n and atherosclerosis. (C) 2001 Elsevier Science B.V. All rights reserved.