LDL-induced macrophage toxicity

Mitchinson, M. J.; Reid, V.C.; Hardwick, Simon J.; Clare, K.; Carpenter, Keri L. H.; Marchant, Christine E.

doi:10.1016/0021-9150(94)94328-1

Cited by 2 publications

(2 citation statements)

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“…45 Lesional M foam cell functional heterogeneity may be influenced by (1) the duration of residence within the lesion; (2) the local microenvironment of stimulatory and inhibitory growth factor and cytokine signals; and (3) regional location within the lesion. For example, Ms at the shoulder of lesions express stromelysin activity selectively, 46 while within the necrotic core of advanced plaques M cell death may be either programmed (apoptosis) 47 or result from toxic accumulation of modified lipoprotein derivatives and nitric oxide or local depletion of M-CSF. 48 There is, however, little evidence that gene expression by lesional Ms in vivo changes cellular behavior or influences the initiation or progression of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Macrophage Phenotype in Mice Deficient in Both Macrophage-Colony–Stimulating Factor (Op) and Apolipoprotein E

Villiers

Smith

Miyata

et al. 1998

ATVB

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Abstract-Mice deficient in both macrophage-colony-stimulating factor (M-CSF, op) and apolipoprotein E (apoE) have elevated cholesterol levels but are protected from atherosclerosis. To assess the contribution of macrophage (M) phenotypic heterogeneity and scavenger receptor (SR-A) expression to this seeming paradox, we characterized the M phenotype by immunohistochemistry in these animals. Lesion size was determined in animals fed a chow or Western-type diet, and lipoprotein clearance studies were performed in vivo. Op0/E0 mice have fourfold smaller aortic root lesions than op2/E0 animals despite 2.5-fold higher total plasma cholesterol levels. Ms in atherosclerotic lesions of op2/E0 mice constitute a predominantly recruited and M-CSF-dependent population.

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Section: Discussionmentioning

confidence: 99%

Macrophage Phenotype in Mice Deficient in Both Macrophage-Colony–Stimulating Factor (Op) and Apolipoprotein E

Villiers

Smith

Miyata

et al. 1998

ATVB

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“…[4][5][6] As to the effects of oxLDL on macrophage viability, however, there are a number of somewhat conflicting reports. [7][8][9][10][11] LDL is a lysosome-destined particle that is typically transported into cells via receptor-mediated endocytosis. Although most cells have LDL receptors on their plasma membrane, the expression of this receptor on macrophages is low.…”

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confidence: 99%

Uptake of Oxidized LDL by Macrophages Results in Partial Lysosomal Enzyme Inactivation and Relocation

Yuan

Olsson

et al. 1998

ATVB

108

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Abstract-The cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells might contribute to atherosclerosis by causing cell death, presumably by both apoptosis and necrosis. After its uptake into macrophage lysosomes by receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in ceroid-containing foam cells. We studied the influence of oxLDL on lysosomal enzyme activity and, in particular, on lysosomal membrane stability and the modulation of these cellular characteristics by HDL and vitamin E (vit-E). Unexposed cells and cells exposed to acetylated LDL (AcLDL) were used as controls. The lysosomal marker enzymes cathepsin L and N-acetyl-␤-glucosaminidase (NA␤Gase) were biochemically assayed in J-774 cells after fractionation. Lysosomal integrity in living cells was assayed by the acridine orange (AO) relocation test. Cathepsin D was immunocytochemically demonstrated in J-774 cells and human monocyte-derived macrophages. We found that the total activities of NA␤Gase and cathepsin L were significantly decreased, whereas their relative cytosolic activities were enhanced, after oxLDL exposure. Labilization of the lysosomal membranes was further proven by decreased lysosomal AO uptake and relocation to the cytosol of cathepsin D, as estimated by light and electron microscopic immunocytochemistry. HDL and vit-E diminished the cytotoxicity of oxLDL by decreasing the lysosomal damage. The results indicate that endocytosed oxLDL not only partially inactivates lysosomal enzymes but also destabilizes the acidic vacuolar compartment, causing relocation of lysosomal enzymes to the cytosol. Exposure to AcLDL resulted in its uptake with enlargement of the lysosomal apparatus, but the stability of the lysosomal membranes was not changed. (Arterioscler Thromb Vasc Biol. 1998;18:177-184.)

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LDL-induced macrophage toxicity

Cited by 2 publications

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Macrophage Phenotype in Mice Deficient in Both Macrophage-Colony–Stimulating Factor (Op) and Apolipoprotein E

Macrophage Phenotype in Mice Deficient in Both Macrophage-Colony–Stimulating Factor (Op) and Apolipoprotein E

Uptake of Oxidized LDL by Macrophages Results in Partial Lysosomal Enzyme Inactivation and Relocation

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