LPS-induced cytokine production and expression of β2-integrins and CD14 by peripheral blood mononuclear cells of patients with homozygous familial hypercholesterolemia

Rovers, C.P.; Netea, Mihai G.; Bont, N. de; Demacker, P.N.M.; Jacobs, Cor; Kullberg, Bart Jan; Meer, J.W.M. van der; Stalenhoef, Anton F. H.

doi:10.1016/s0021-9150(98)00152-x

Cited by 31 publications

(19 citation statements)

References 26 publications

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“…Hyperresponsiveness of macrophages from hyperlipoproteinemic individuals to this stimulation may prove a highly deleterious event for the subsequent development of atherosclerosis. In this respect, we have recently reported that macrophages isolated from hyperlipoproteinemic LDLR Ϫ/Ϫ mice (36), as well as PBMC from homozygous patients with familial hyperlipoproteinemia (FH) (37), are also hyperresponsive to LPS stimulation.…”

Section: Discussionmentioning

confidence: 99%

“…However, our experiments have demonstrated only a modest increase of 19% in the CD14 expression after incubation of cells with nLDL, which is unlikely to account for the several-fold increase in cytokine production after LPS challenge. Moreover, monocytes of familial hypercholesterolemia patients express normal amounts of CD14 (37,42), and the increased cytokine production after LPS stimulation of macrophages isolated from LDLR Ϫ/Ϫ mice is CD14-independent (36). The cytokine production in macrophages from LDLR Ϫ/Ϫ mice is mediated through CD11c/CD18 (36), which is the second possible LPS co-receptor (43).…”

Section: Discussionmentioning

confidence: 99%

“…As the stimulatory action of nLDL on cytokine production has also been documented in vivo in LDLR Ϫ/Ϫ mice and homozygous patients with familial hypercholesterolemia (36,37), it is unlikely that this effect is mediated through the LDL receptor. Alternatively, preliminary data from our laboratory (Netea et al, unpublished results) suggest that the intracellular events leading to an increased responsiveness to a LPS challenge are triggered by a modification of cell membrane fluidity by nLDL, as others have also suggested (46).…”

Section: Discussionmentioning

confidence: 99%

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Native LDL potentiate TNFα and IL-8 production by human mononuclear cells

Netea

Kullberg

Demacker

et al. 2002

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Native LDL potentiate TNFα and IL-8 production by human mononuclear cells

Netea

Kullberg

Demacker

et al. 2002

Journal of Lipid Research

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“…Corresponding with this observation, Gram-negative LPS (from E. coli) induced lipid accumulation and foam cell formation from macrophages in vitro, 32 a mechanism that may explain increased plaque formation demonstrated in vivo by our group and others. 13,[33][34][35][36] Other bacterial components, such as Chlamydia heatshock protein (cHSP) 60, were shown to be associated with the presence of CPN in atheromatous plaques. 37 Kol et al 38,39 demonstrated that cHSP 60 has been localized in human atheroma and activated human vascular endothelium, smooth muscle cells, and macrophages.…”

Section: Discussionmentioning

confidence: 99%

Chronic perivascular inoculation with Chlamydophila pneumoniae results in plaque formation in vivo

Engelmann

Redl

Pelisek

et al. 2006

Laboratory Investigation

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Hypercholesterolemic and normocholesterolemic rabbit models of chronic arterial Chlamydophila (Chlamydia) pneumoniae (CPN) inoculation were established and the role of both viable and inactivated bacteria was investigated in atherogenesis. A total of 29 rabbits were randomized to four groups. Groups A and B were fed a cholesterol-enriched diet, and groups C and D were fed a normal diet. Arterial segments of group A and C animals were inoculated in vivo using viable CPN chronically using repeated perivascular applications. Contralateral arteries were treated using heat-inactivated CPN. Group B and D animals were treated with repeated perivascular injections of bacterial lipopolysaccharide (LPS) and saline (control). Additional hypercholesterolemic rabbits were treated by repeated injections using viable and inactivated CPN, each controlled by saline injections. To compare the effects of this chronic inoculation model, additional animals received single injections of either viable CPN, inactivated CPN, LPS, or saline. Vascular tissues (n ¼ 162 treated arteries of 29 rabbits) were analyzed using morphometry at histology. CPN was detected by fluorescenceimmunohistochemistry and nested polymerase chain reaction. Only in hypercholesterolemic, but not in normocholesterolemic rabbits, chronic perivascular infection of all bacterial components, viable and heatinactivated CPN, as well as LPS resulted in a significant increase in atheromatous lesion formation (lesion area index: 0.2370.08, 0.2570.09, and 0.1570.05) when compared to controls (lesion area index 0.0170.01, P ¼ 0.002). CPN persisted in atheromatous lesions and vascular tissues. Single perivascular infection using CPN or inactivated CPN was not able to induce lesion formation (lesion area index: 0.0370.03, 0.0370.02 vs 0.0370.02 after single saline inoculation, P ¼ 0.965). In conclusion, chronic vascular infection with CPN or CPN components acts as a cofactor requiring other major atherogenic stimuli, rather than as a causative agent.

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“…5 Gram-negative LPS (from E. coli as well as C. pneumoniae) induces lipid accumulation and foam cell formation from macrophages in vitro, 4,23 a mechanism that might explain increased lesion formation demonstrated in vivo by our group and others. 6,[15][16][17]24 Recently, tolllike receptor 4, the receptor recognizing bacterial LPS, was identified in adventitial fibroblasts and macrophages in human atherosclerotic plaques and was shown to augment neointima formation in a mouse model of adventitial delivery of LPS. 25 In addition, the oxidative modification of low-density lipoprotein is enhanced by LPS.…”

Section: Discussionmentioning

confidence: 99%

Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo

Engelmann

Redl

Nikol

2004

Laboratory Investigation

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Bacteria and viruses are suspected to induce arteriosclerosis; however, most investigators have focused on coincidences rather than causal relationships. The aim of this work was to establish a rabbit model in which the vessel reaction to local perivascular injection of defined bacterial products can be analyzed. A total of 23 rabbits were randomized to four groups. Groups A and B were fed a normal diet, groups C and D were fed a cholesterolenriched diet. Groups A and C were treated with a single perivascular injection of bacterial lipopolysaccharide (LPS, endotoxin) placed next to auricular, carotid and femoral arteries, and sodium chloride placed next to the contralateral arteries (control). Group B and D animals were treated with repeated perivascular injections over 90 days. Vascular tissues (n ¼ 116 treated segments of 23 rabbits) were analyzed using morphometry at histology, and using immunohistochemistry to detect macrophages, lymphocytes and vascular smooth muscle cells. LPS treatment resulted in transient focal intima thickening. After single LPS application, no increase in atheromatous lesion formation was observed in comparison with controls (group C, lesion area index 0.03170.012 vs 0.01570.006, P ¼ 1.0). Repeated LPS application resulted in significant atheromatous lesion formation compared with saline control (group D, lesion area index 0.14870.049 vs 0.00870.006, P ¼ 0.003) in hypercholesterolemic rabbits. Repeated LPS inflammation in normocholesterolemic did not lead to atheromatous lesion formation (intima media ratio 0.0470.01 vs 0.0470.007, P ¼ 1.0). Single perivascular administration of low-dose bacterial LPS resulted in transient focal intimal thickening, while significant increase in lesion formation occurred after repeated LPS application in cholesterol-fed animals. In conclusion, this animal model will allow the assessment of the impact of defined dosages of different bacterial pathogens onto the vascular wall in the context of atherogenesis. The atheromatous lesion-promoting effect of repeated perivascular administration of LPS supports the hypothesis that bacterial pathogens may be involved in atherogenesis.

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LPS-induced cytokine production and expression of β2-integrins and CD14 by peripheral blood mononuclear cells of patients with homozygous familial hypercholesterolemia

Cited by 31 publications

References 26 publications

Native LDL potentiate TNFα and IL-8 production by human mononuclear cells

Native LDL potentiate TNFα and IL-8 production by human mononuclear cells

Chronic perivascular inoculation with Chlamydophila pneumoniae results in plaque formation in vivo

Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo

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