The oxidative modification of low density lipoprotein by human lymphocytes

Lamb, David; Wilkins, Gary M.; Leake, David S.

doi:10.1016/0021-9150(92)90277-n

Cited by 67 publications

(24 citation statements)

References 16 publications

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“…50 In conclusion, the data reported in this study provide strong evidence in favor of an enhanced and specific oxidation of LDL in patients with advanced carotid atherosclerosis and raise at least two essential questions concerning (1) the biological mechanisms promoting the oxidative process and (2) their relevance to the progression of the atherosclerotic disease. It is conceivable that inflammatory cells present within the advanced atherosclerotic lesions may represent the sources of oxygenreactive species causing the peroxidation of LDL lipids, and the demonstrations that lymphocytes can oxidize LDL 51 and that anti-oxLDL autoantibodies are present in patients with chronic aortitis 43 are in agreement with this view. Furthermore, a correlation between the antioxidatively modified LDL autoantibody titer and the extent and severity of inflammatory reactions within the atherosclerotic plaque can be predicted, together with a possible beneficial effect of antioxidant supplementation in protecting against plaque complication.…”

mentioning

confidence: 74%

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Maggi

Chiesa

Melissano

et al. 1994

Arterioscler Thromb

189

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Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO 4 . However, vitamin E efficiency was lower (9.6±4.2 versus 30.2±7.6 min/ nmol vitamin E) and the duration of the vitamin E-independent lag phase was longer (105.5±16.5 versus 58± 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu 2+ -oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other C arotid atherosclerosis, ranging from intima-media thickening to the appearance of more advanced lesions such as fibrotic and complicated plaques, affects about 25% of the whole population.

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mentioning

confidence: 74%

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Maggi

Chiesa

Melissano

et al. 1994

Arterioscler Thromb

189

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“…If it is also chemotactic for monocytes, there could be an interaction in which T cells help recruit additional macrophages, and vice versa. Furthermore, lymphocytes themselves have recently been shown capable of oxidizing LDL (38). Thus, there could be an important interplay between T lymphocytes and macrophages, accelerating both the oxidative modification of LDL and the recruitment of additional T lymphocytes and monocytes.…”

Section: Resultsmentioning

confidence: 99%

Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes.

McMurray¹,

Parthasarathy²,

Steinberg³

1993

J. Clin. Invest.

245

112

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Oxidatively modified low density lipoprotein (Ox-LDL) is a known chemoattractant for monocytes. Here we demonstrate, using a modified Boyden chamber assay, that human peripheral blood T lymphocytes, but not B lymphocytes, also respond chemotactically to Ox-LDL, showing a threefold increase over control and an optimum response at 10 ;tg/ml. Copper and endothelial cell-oxidized LDL and #l-VLDL were used and gave similar results. The activity was not chemokinetic and native LDL possessed no chemoattractant activity. The chemoattractant activity was found to reside in the lipid fraction of Ox-LDL. Lysophosphatidylcholine is a major phospholipid component of Ox-LDL and is known to be chemotactic for monocytes. We show that lysophosphatidylcholine is also chemotactic for T lymphocytes with a maximal fourfold increase at 10 MM. Nonmetabolizable analogues of lysophosphatidylcholine had no such chemotactic effect. Thus, Ox-LDL, by virtue of its lysophosphatidylcholine content, may contribute to the recruitment of both T lymphocytes and monocytes into developing atherosclerotic lesions. (J. Clin. Invest. 1993. 92:1004-1008

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“…Although the precise molecular mechanism(s) underlying oxidative LDL modification in vivo remains unknown, in vitro studies on cell-mediated LDL oxidation are generally carried out in medium containing small amounts of the transition metals iron and/or copper. Under these conditions all cell types present in a lesion (i.e., endothelial cells [3], macrophages [4], smooth muscle cells [5,6] and lymphocytes [7]) are capable of oxidizing LDL. Where investigated directly, in vitro cell-mediated LDL oxidation has been shown to have an absolute requirement for the presence ofiron and copper in the medium (3,6); i.e., in their absence, these cells do not oxidize LDL lipids substantially.…”

Section: Introductionmentioning

confidence: 99%

Inhibition by interferon-gamma of human mononuclear cell-mediated low density lipoprotein oxidation. Participation of tryptophan metabolism along the kynurenine pathway.

Christen¹,

Thomas²,

Garner³

et al. 1994

J. Clin. Invest.

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In this study we examined the potential inhibition by interferon-y (IFN'y) of the early stages of low density lipoprotein (LDL) oxidation mediated by human peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages (NMDMN) in Ham's F-10 medium supplemented with physiological amounts of L-tryptophan (Trp). We assessed LDL oxidation by measuring the consumption of LDL's major antioxidant (i.e., a-tocopherol) and targets for oxidation (cholesteryllinoleate and cholesterylarachidonate), together with the accumulation of cholesterylester hydroperoxides and the increase in relative electrophoretic mobility of the lipoprotein particle. Exposure of PBMC or MDM to IFNy induced the degradation of extracellular Trp with concomitant accumulation of kynurenine, anthranilic and 3-hydroxyanthranilic acid (3HAA) in the culture medium. Formation of 3HAA, but neither Trp degradation nor formation ofkynurenine and anthranilic acid, was inhibited by low amounts of diphenylene iodonium (DPI) in a concentration-dependent manner. In contrast to oxidative Trp metabolism, exposure of human PBMC or MDM to IFN-y failed to induce degradation ofarginine, and nitrite was not detected in the cell supernatant, indicating that nitric oxide synthase was not induced under these conditions. Incubation of LDL in Trpsupplemented F-10 medium resulted in a time-dependent oxidation of the lipoprotein that was accelerated in the presence of PBMC or MDM but inhibited strongly in the presence of both cells and IFNy, i.e., when Trp degradation and formation of 3HAA were induced. In contrast, when IFNy was added to PBMC or MDM in F-10 medium that was virtually devoid of Trp, inhibition of cell-accelerated LDL oxidation was not observed. Exogenous 3HAA added to PBMC or purified monocytes in the absence of IFNy also strongly and in a concentration-dependent manner inhibited LDL oxidation. Selective inhibition of IFNy-induced formation of 3HAA by DPI caused reversion of the inhibitory action of this cytokiine on both PBMC-and MDM-mediated LDL oxidation. These results show that IFN'y treatment of human PBMC or MDM in vitro attenuates the extent of LDL oxidation caused by these cells,

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The oxidative modification of low density lipoprotein by human lymphocytes

Cited by 67 publications

References 16 publications

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Oxidatively modified low density lipoprotein is a chemoattractant for human T lymphocytes.

Inhibition by interferon-gamma of human mononuclear cell-mediated low density lipoprotein oxidation. Participation of tryptophan metabolism along the kynurenine pathway.

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