LDL AND ACETYL-LDL INHIBIT THE NK ACTIVITY AND ARE TAKEN UP BY CD56(+) LYMPHOCYTES

The effect of LDL and modified LDL (acetyl-LDL) was studied on human n atural killer cell-mediated cytotoxicity against K562 cells. Incubatio n for 24 h of peripheral blood lymphocytes (PBL) with a high concentra tion (200 mu g/ml) of LDL decreased the NK activity in some donors. Af ter acetylation of the LDL protein (apoB), the modified-LDL systematic ally inhibited the NK function of PBL in a time- and dose-dependent ma nner. Inhibition mediated by acetyl-LDL (AcLDL) was significantly grea ter than that of LDL, indicating that the apoB modification can mediat e the inhibition of the NK function. AcLDL also inhibited the NK activ ity of peripheral blood mononuclear cells, suggesting that, under our experimental conditions, monocytes are not efficient enough to protect NK cells against the adverse effects of modified-LDL. With a cytofluo rimetric analysis, the internalization of acetyl-LDL by PBL was demons trated and was only 3-4 times lower than LDL internalization in lympho cytes. It appeared to be time, temperature and dose dependent, saturab le and different from the internalization mediated by the known scaven ger receptors. Finally, CD14(-) CD3(+) lymphocytes and CD14(-) CD56(+) lymphocytes were able to internalize AcLDL in the same way. Our resul ts suggest that in some in vivo circumstances, when the LDL concentrat ion and/or the modified-LDL/LDL ratio increase in tissues, lipoprotein s are internalized by NK cells and also can induce adverse effects on the NK function.