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 natural killer cell-mediated cytotoxicity against K562 cells. Incubation for 24 h of peripheral blood lymphocytes (PBL) with a high concentration (200 micrograms/ml) of LDL decreased the NK activity in some donors. After acetylation of the LDL protein (apoB), the modified-LDL systematically inhibited the NK function of PBL in a time- and dose-dependent manner. Inhibition mediated by acetyl-LDL (AcLDL) was significantly greater than that of LDL, indicating that the apoB modification can mediate the inhibition of the NK function. AcLDL also inhibited the NK activity 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 cytofluorimetric analysis, the internalization of acetyl-LDL by PBL was demonstrated and was only 3-4 times lower than LDL internalization in lymphocytes. It appeared to be time, temperature and dose dependent, saturable and different from the internalization mediated by the known scavenger receptors. Finally, CD14- CD3+ lymphocytes and CD14- CD56+ lymphocytes were able to internalize AcLDL in the same way. Our results suggest that in some in vivo circumstances, when the LDL concentration and/or the modified-LDL/LDL ratio increase in tissues, lipoproteins are internalized by NK cells and also can induce adverse effects on the NK function.
Juompan
L
L
INSERM U 395, Université Paul Sabatier, Faculté de Médecine Purpan, Toulouse, France.
Fournié
G J
GJ
Benoist
H
H
D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D019002:CD56 Antigen; D015815:Cell Adhesion Molecules; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D011973:Receptors, LDL / Q000032:analysis; D051116:Receptors, Scavenger
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D015815:Cell Adhesion Molecules; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D051116:Receptors, Scavenger; C032629:acetyl-LDL