Phospholipid methylation and phospholipase A2 activation in cytotoxicity by human natural killer cells.
The role of phospholipid methylation and phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) in natural killer (NK) function by human peripheral blood mononuclear cells was studied. Pretreatment of effector cells with a methyltransferase inhibitor, 3-deazaadenosine, in the presence of homocysteine thiolactone, reduced cytotoxicity in a dose-dependent fashion. This effect was closely associated with inhibition of methylation of lipids but not of nucleic acids or proteins. The suggestion for a role of phospholipid methylation was supported by the observation that the interaction between NK-susceptible tumor targets and peripheral blood mononuclear cells caused increased phospholipid methylation only when susceptible target cells were used. Phospholipase A2 was also implicated in human NK activity. Inhibitors of the enzyme such as tetracaine, mepacrine, Rosenthal's inhibitor, and corticosteroids impaired NK function. Rosenthal's inhibitor was also shown to exert an inhibitory effect on a purified NK-cell population obtained by the isolation of large granular lymphocytes on Percoll gradients. Peripheral blood mononuclear cells were also directly shown to display phospholipase A2-like activity, as measured by the decrease in radioactive arachidonate from prelabeled phospholipids, specifically phosphatidylcholine, in effector cells. These data suggest that enhanced phospholipid methylation occurs during the recognition function of NK cells. Consequent activation of phospholipase A2 might be involved in the mechanisms leading to lytic events within the target cell.
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D001095:Arachidonic Acids / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004789:Enzyme Activation; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007694:Killer Cells, Natural / Q000502:physiology*; D008745:Methylation; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010743:Phospholipids / Q000378:metabolism*; D014372:Tubercidin / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D001095:Arachidonic Acids; D010743:Phospholipids; C018258:3-deazaadenosine; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D014372:Tubercidin