EFFECT OF LIPOPOLYSACCHARIDE ON MITOGEN-ACTIVATED PROTEIN-KINASES AND CYTOSOLIC PHOSPHOLIPASE A(2)

The addition of platelet-activating factor (PAF) to human neutrophils increases phosphorylation on tyrosine residues and stimulates the activity of p42(erk2)mitogen-activated protein kinase (MAP kinase). This action is rapid and transient. In contrast, p42(erk2), p44(erk1) and the p40(hera) MAP kinase isoforms are all not tyrosine phosphorylated or activated in human neutrophils stimulated with low concentrations of lipopolysaccharide (LPS) in combination with serum. In spite of this, the PAF-induced tyrosine phosphorylation and activation of the p42(erk2) MAP kinase are greatly potentiated in cells pretreated with LPS. More interestingly, although low concentrations of LPS do not affect MAP kinase isoforms in these cells, they cause the phosphorylation of cytosolic phospholipase A(2) (cPLA(2)), as evidenced by a decrease in the electrophoretic mobility of the enzyme. In addition, this stimulus-induced upward shift in the mobility of the enzyme is not inhibited by the tyrosine kinase inhibitor, genistein. Furthermore, LPS increases the release of arachidonic acid in control and PAF-stimulated human neutrophils. These observations clearly show that cPLA(2) can be phosphorylated and activated by kinases other than the currently known MAP kinases. It is proposed that there are MAP kinase-dependent and -independent mechanisms for the phosphorylation of cPLA(2).