Phospholipid methylation andphospholipase A2activation in cytotoxicity byhumannatural killer cells

Therole ofphospholipid methylation andphos- pholipase A2(phosphatide 2-acylhydrolase, EC3.1.1.4) innatural killer (NK) function byhumanperipheral blood mononuclear cells wasstudied. Pretreatment ofeffector cells with amethyltransfer- aseinhibitor, 3-deazaadenosine, inthepresence ofhomocysteine thiolactone, reduced cytotoxicity inadose-dependent fashion. This effect wasclosely associated withinhibition ofmethylation oflipids butnotofnucleic acids orproteins. Thesuggestion for arole ofphospholipid methylation wassupported bytheobser- vation that theinteraction between NK-susceptible tumor targets andperipheral blood mononuclear cells caused increased phos- pholipid methylation only whensusceptible target cells wereused. Phospholipase A2wasalso implicated inhumanNKactivity. In- hibitors oftheenzyme such astetracaine, mepacrine, Rosenthal's inhibitor, andcorticosteroids impaired NKfunction. Rosenthal's inhibitor wasalso shown toexert aninhibitory effect onapurified NK-cell population obtained bytheisolation oflarge granular lym- phocytes onPercoll gradients. Peripheral blood mononuclear cells werealso directly shown todisplay phospholipase A2-like activity, asmeasured bythedecrease inradioactive arachidonate from prelabeled phospholipids, specifically phosphatidylcholine, inef- fector cells. These data suggest that enhanced phospholipid meth- ylation occurs during therecognition function ofNKcells. Con- sequent activation ofphospholipase A2might beinvolved inthe mechanisms leading tolytic events within thetarget cell. Transmethylation,