Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages: Regulation by Group IV cytosolic phospholipase A 2, but not by Group V and Group IIA secretory phospholipase A 2

Abstract

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 Ca 2+ 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 2). LPS has no effect on the levels of Groups V and IIA 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.