Trp-Lys-Tyr-Met-Val-D-Met stimulates superoxide generation and killing of Staphylococcus aureus via phospholipase D activation in human monocytes

Among the phagocytic leukocytes, monocytes have the important role of clear ing out parasitic microorganisms, They accomplish this through production o f toxic metabolites of oxygen, Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), a peptid e that stimulates phosphoinositide (PI) hydrolysis in human leukocytes, inc luding monocytes, binds to a unique cell surface receptor and stimulates su peroxide generation, killing of Staphylococcus aureus, and activation of ph ospholipase D (PLD) in human monocytes. Preincubation of the cells with a P I-specific phospholipase C (PLC) inhibitor (U-73122), protein kinase C inhi bitor (GF109203X), or intracellular Ca2+ chelator (BAPTA/AM) before the pep tide stimulus totally inhibits the peptide-induced PLD activation and super oxide generation. On the other baud, tyrosine kinase inhibitor genistein on ly partially inhibits the peptide-induced processes, The peptide-induced ba cteria killing activity shares regulatory mechanisms for PLD activation wit h the superoxide generation, which is inhibited in the presence of l-butano l, We suggest that the peptide stimulates PLD downstream of PLC activation and PLD activation in turn is essential for the peptide-induced immunologic al functions such as the superoxide generation and killing of bacteria by h uman monocytes.