Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages:: Regulation by Group IV cytosolic phospholipase A2, but not by Group V and Group IIA secretory phospholipase A2

Lipopolysaccharide (LPS) induces a delayed release (lag phase of 2-4 h) of arachidonic acid (AA) and prostaglandin (PG) D-2 in rat liver macrophages. Group IV cytosolic phospholipase A(2) (cPLA(2)) becomes phosphorylated within minutes after the addition of LPS. The phosphorylated form of cPLA(2) shows an enhanced in vitro activity. The Ca2+ dependence of cPLA(2) activity is not affected by phosphorylation of the enzyme. In addition, LPS induces an enhanced expression of cPLA(2) mRNA (after 2-4 h) and an enhanced expression of cPLA(2) protein (after 8 h). The cellular cPLA(2) activity is enhanced about twofold 24 h after LPS treatment. Liver macrophages constitutively express mRNAs encoding Groups V and IIA secretory PLA(2) (sPLA,). LPS has no effect on the levels of Groups V and HA sPLA(2) mRNA expression. Despite mRNA expression, Groups V and IIA sPLA(2) protein and sPLA(2) activity are not detectable in unstimulated or LPS-stimulated liver macrophages. Collectively, these and earlier [Mediators Inflammation 8 (1999) 295.] results suggest that in liver macrophages the LPS-induced delayed release of AA and prostanoids is mediated by phosphorylation and an enhanced expression of cPLA(2), a de novo expression of cyclooxygenase (COX)-2, but not by the actions of Group V or Group IIA sPLA(2). (C) 2002 Elsevier Science Inc. All rights reserved.