BIOCHEMISTRY AND CELL BIOLOGY OF PHOSPHOLIPASE-D IN HUMAN NEUTROPHILS

Neutrophils play a major role host defense against invading microbes. Recent studies have emphasized the importance of the phospholipase D ( PLD) in the signalling cascade leading to neutrophil activation. Phosp holipase D catalyzes the hydrolysis of phospholipids to generate phosp hatidic acid with secondarily generation of diradylglycerol; both of t hese products have been implicated as second messengers. Herein, we di scuss the regulation and the biochemistry of the receptor-regulated PL D in human neutrophils. In vivo and in vitro studies suggest an activa tion mode in which initial receptor-linked activation of phospholipase C generates diacylglycerol and inositol trisphosphate. The resulting calcium flux along with the diacylglycerol activate a conventional iso form of protein kinase C (PKC), probably PKC beta 1. This PKC, in turn phosphorylates a plasma membrane component resulting in PLD activatio n and a second outpouring of diradylglycerol. The small GTP-binding pr oteins, RhoA and ARF, also participate in this process, and synergize with a 50 kDa cytosolic regulatory factor.