Phosphoinositide breakdown and evidence for protein kinase C involvement during human NK killing

Conjugation between human NK cells and susceptible target cells (K562 and Jurkat) leads to breakdown of inositol lipids in the effector cells but not when conjugated with resistant target cells. Extracellular Ca2+ is required for this activation. Sphingosine inhibits NK killing in both normal and IL-2-activated NK cells. Phorbol esters, TPA, and PDBU enhanced NK killing at low concentrations, where 4-alpha-PDIDE did not. The diacylglycerol derivative OAG increased NK cell killing and activated PKC from human lymphocytes. These results strongly suggest that phosphoinositide breakdown and activation of PKC is involved in NK killing.