Low-Density Lipoprotein Oxidized by Polymorphonuclear Leukocytes Inhibits Natural Killer Cell Activity

Abstract

We studied the effect of low-density lipoprotein (LDL) oxidized by opsonized zymosan-stimulated polymorphonuclear leukocytes (PMN) on natural killer (NK) cell activity. Oxidized LDL inhibited NK cell activity in a dose-dependent manner, whereas normal LDL left it unaffected. However, oxidized LDL did not inhibit antibody-dependent cell-mediated cytotoxicity (ADCC). Moreover, a positive correlation was observed between the amount of thiobarbituric acid-reacting substances (TBARS) on the sample of oxidized LDL and the degree of inhibition of NK cell activity. We also showed that oxidized LDL suppressed the binding capacity of purified large granular lymphocytes (LGL) to target cells without changing the lytic activity. These results therefore suggest that activated PMN can modulate NK cell activity by oxidizing LDL.

Structural changes of high‐density‐lipoprotein apolipoproteins following incubation with human polymorphonuclear cells

“…Thus, the a-tocopherol content was sufficient to protect HDL from lipid peroxidation, despite oxidative stress. These finding are consistent with previous studies, which showed that PMN caused less oxidation of HDL than of LDL [32]. However, a recent study of HDL oxidation using chemical oxidizing systems (Cu'+) detected no large variations in classical oxidative monitors such as TBARS, even though oxidized cholesterol derivatives emerged [33].…”

Low density lipoprotein receptor expression and function in human polymorphonuclear leucocytes

“…On the other hand, a delayed clearance of LDL from the plasma due to unimpaired receptor function renders this molecule more susceptible to modifications which have been demonstrated to be involved in the transformation of macrophages to foam cells [1][2][3]. Recently, several reports [3][4][5][6]8] have shown that free radicals produced by stimulated PMN and macrophages (N-formyl-L-methionyl-Lleucyl-L-phenylalanine (fMLP), PMA, or zymosan) avidly modified LDL. This oxLDL is overlooked by normal LDLR interacting only with scavenger receptors [3,11].…”

“…This oxLDL is overlooked by normal LDLR interacting only with scavenger receptors [3,11]. OxLDL altered lymphocyte and macrophage proliferative and cytotoxic responses [3][4][5][6][7][8], suggesting that this is one of the key physiopathological events in atheroma formation.…”

“…However, several reports [4][5][6][7] have shown that LDL activated monocyte oxidative metabolism and lysosomal enzyme release. These effects were inhibited by interferon-gamma (IFN-) [8]. LDL and modified LDL also altered T lymphocyte proliferative response [1,3] and natural killer (NK) proliferative and cytotoxic responses [9,10].…”

“…LDL and modified LDL also altered T lymphocyte proliferative response [1,3] and natural killer (NK) proliferative and cytotoxic responses [9,10]. Polymorphonuclear neutrophils (PMN) are involved indirectly in the formation of the atheroma, since their secretion upon activation of myeloperoxidase (MPO) and free radicals is able to modify LDL, rendering it prone to atheroma formation [3,8,11,12]. In cardiac reperfusion injury, PMN are important in the progress of atherosclerotic lesions observed in these patients [11].…”