NOVEL GROUP-V PHOSPHOLIPASE A(2) INVOLVED IN ARACHIDONIC-ACID MOBILIZATION IN MURINE P388D(1) MACROPHAGES

Four related genes encode four different secretory phospholipase A(2) (sPLA(2)) enzymes in mammals, namely the well described Group I and II A enzymes and the more recently described Groups IIC and V. A large bo dy of research has putatively demonstrated that the Group IIA sPLA(2) is involved in diverse pathologic processes, such as rheumatoid arthri tis, septic shock, intestinal neoplasia, and epidermal hyperplasia, as well as in cellular signaling by regulating the formation of arachido nate-derived lipid messengers, However, we demonstrate herein the invo lvement of another sPLA(2), i.e. the Group V sPLA(2), in arachidonic a cid release and prostaglandin production in the mouse macrophage-like cell line P388D(I). Abundant message for Group V sPLA(2) was detected in both resting and activated cells, In contrast, Group IIA sPLA(2) me ssage was undetectable as analyzed by Northern blot and reverse transc riptase-polymerase chain reaction, Moreover, blockage of Group V sPLA( 2) gene expression by antisense RNA oligonucleotides resulted in inhib ition of prostaglandin E(2) production as well as reduction of the amo unt of sPLA(2) protein at the cellular surface, Collectively, these re sults uncover Group V sPLA(2) as a novel effector involved in arachido nic acid-mediated signal transduction.