Identification of low density lipoprotein as a regulator of Fc receptor-mediated phagocytosis.

Bigler, Robert D.; Khoo, Maureen; Lund‐Katz, Sissel; Scerbo, L.; Esfahani, Mohammad Reza

doi:10.1073/pnas.87.13.4981

Cited by 22 publications

(19 citation statements)

References 29 publications

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“…1 Macrophage differentiation in plaques is associated with expression of Fas-L and iNOS. 6,33 If our in vitro system is related to these findings in plaques, then proapoptotic activation should be dependent on culture lipoproteins (which occurs normally in fetal calf serum 20 ), and on scavenger receptors, which was confirmed. Furthermore, this model predicts that plaque macrophages should express TNF-␣ and plaque VSMCs should express TNF-R1, which we also confirmed.…”

Section: Discussionmentioning

confidence: 91%

“…Incubation in LPDFCS consistently reduced the spontaneous expression of surface Fas-L and TNF-␣ by isolated, cultured macrophages at maturation day 8 (online Figure IIIA and IIIB). Importantly, the addition of physiologic levels of LDL (0.2 mg/mL) 20 reconstituted the typical expression of surface Fas-L and TNF-␣ by isolated macrophages at culture day 8 (online Figure IIIC). In addition, the scavenger receptor ligands acetyl-LDL, maleyl-bovine serum albumin, and polyinosine (but not polycytosine, a recognized control for polyinosine 21 ) stimulated macrophage surface Fas-L and TNF-␣ expression (online Figure IIID-IIIG).…”

Section: Macrophage Tnf-␣ Expression Is Dependent On Medium Lipoproteinsmentioning

confidence: 99%

“…We therefore examined the role of lipoproteins in TNF-␣-associated macrophage activation. We examined TNF-␣ and Fas-L surface expression, nitrite efflux, and VSMC apoptosis in macrophages cultured in control medium or in medium constituted with lipoprotein-depleted fetal calf serum (LDFCS), as described 20 Incubation in LDFCS had no effect on macrophage survival (data not shown) but reduced both macrophage-induced plaque VSMC apoptosis (apoptotic index, meanϮSEM: control, 72Ϯ5%; LDFCS, 25Ϯ3.4%) and nitrite efflux (control, 438Ϯ56 nmol nitrite; LDFCS, 290Ϯ20 nmol nitrite; PϽ0.05). Incubation in LPDFCS consistently reduced the spontaneous expression of surface Fas-L and TNF-␣ by isolated, cultured macrophages at maturation day 8 (online Figure IIIA and IIIB).…”

Section: Macrophage Tnf-␣ Expression Is Dependent On Medium Lipoproteinsmentioning

confidence: 99%

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Tumor Necrosis Factor-α Promotes Macrophage-Induced Vascular Smooth Muscle Cell Apoptosis by Direct and Autocrine Mechanisms

Boyle

Weissberg

Bennett

2003

ATVB

172

115

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Objective-We have previously shown that human macrophages induce human plaque vascular smooth muscle cell (VSMC) apoptosis by cell-cell proximity, Fas-L, and nitric oxide (NO), thereby predisposing to plaque rupture. This study sought to analyze whether tumor necrosis factor-␣ (TNF-␣) contributes additionally to macrophage-induced VSMC apoptosis. Methods and Results-Macrophage-induced VSMC apoptosis was examined in direct coculture. Antagonistic antibodies to TNF-receptor (R1) inhibited VSMC apoptosis, and preincubation of monocytes and VSMCs indicated that TNF-R1 on both cell types contributed to macrophage-induced VSMC apoptosis. Correspondingly, both monocytes and VSMCs expressed TNF-R1, and macrophages expressed cell surface TNF-␣. Two NO donors upregulated VSMC surface TNF-R1, and exogenous TNF-␣ induced VSMC apoptosis synergistically with the NO donor diethylenetriamine/NO, indicating that NO sensitizes VSMCs to TNF-␣. Neutralizing anti-TNF-R1 antibodies inhibited macrophage activation assessed by Fas-L expression and NO secretion. Key Words: macrophages Ⅲ plaque rupture Ⅲ vascular smooth muscle cells Ⅲ apoptosis Ⅲ tumor necrosis factor A therosclerotic plaque rupture causes myocardial infarction. 1,2 Plaque ruptures are associated with increased fibrous cap macrophages, reduced fibrous cap vascular smooth muscle cells (VSMCs), and increased VSMC apoptosis. [3][4][5] Because VSMCs are the only cells within plaques capable of synthesizing structurally important collagen isoforms, VSMC apoptosis might promote plaque rupture. 4,5 We have shown previously that cultured, human blood monocyte-derived macrophages induce human VSMC apoptosis by direct cell-cell contact, Fas-L/Fas, and nitric oxide (NO). 6,7 Macrophages produce other proapoptotic factors, including the Fas-L homologue tumor necrosis-factor-␣ (TNF-␣). 6 TNF-␣, like Fas-L, has a bioactive, membrane-bound pro-form that mediates cell-cell contact-dependent apoptosis both in vitro 8,9 and in vivo. 10 Although the mechanism by which TNF-␣ acts in cytotoxicity is less clear, there is evidence that it induces VSMC apoptosis synergistically, with the inflammatory cytokines interleukin-1␤ and interferon-␥. 11 TNF-␣ acts through 2 receptors, TNF-R1 and TNF-R2. 12 Both TNF-R1 and TNF-R2 are homologous to Fas. 13,14 Like Fas, TNF-R1 has a death domain that initiates assembly of a death-induced signaling complex, thus activating caspases. 13 TNF-R2 is homologous to TNF-R1 and Fas but lacks a death domain. 13 The mechanism for the proapoptotic effect of TNF-R2 is uncertain. TNF-R2 might, like TNF-R1, by way of tumor necrosis factor receptor-associated factor (TRAF) adaptor molecules, 13 produce proapoptotic effects. Indeed, TNF-R1 and TNF-R2 cooperatively interact to induce apoptosis through TRAFs. 15 Alternatively, Grell et al 12 have postulated that TNF-R2 might mediate the proapoptotic effects of TNF by ligand passing to TNF-R1. Furthermore, macrophage-derived TNF-␣ might activate macrophages in an autocrine loop. 16 -18 Although this could promote cytotoxic...

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Section: Discussionmentioning

confidence: 91%

Section: Macrophage Tnf-␣ Expression Is Dependent On Medium Lipoproteinsmentioning

confidence: 99%

Section: Macrophage Tnf-␣ Expression Is Dependent On Medium Lipoproteinsmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Necrosis Factor-α Promotes Macrophage-Induced Vascular Smooth Muscle Cell Apoptosis by Direct and Autocrine Mechanisms

Boyle

Weissberg

Bennett

2003

ATVB

172

115

View full text Add to dashboard Cite

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“…LDL-C, indeed, has been reported to affect host immune functions. LDL is required for the optimal expression of the Fc receptor or CD14, which mediates phagocytosis of human monocytes, and a high-fat diet has been shown to decrease the antitumor activity of macrophages in mice [19,20,21]. Moreover, high LDL levels have been reported to inhibit T-cell proliferation [22].…”

Section: Discussionmentioning

confidence: 99%

Serum Lipid Profile in Colorectal Cancer Patients with and without Synchronous Distant Metastases

et al. 2005

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Objective: In this study, the serum lipid profile, including total cholesterol (TC), triglycerides (TG), high-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C), has been investigated in colorectal cancer patients (CRC) with and without synchronous distant metastases. The aim of this study was to verify whether the presence of metastases was associated to serum lipid abnormalities, and whether lipoprotein abnormalities were linked to the nutritional status. Methods: The fasting serum lipid profile was examined in 84 CRC patients using colorimetric methods. To determine the nutritional status, the body mass index (BMI) was calculated and serum albumin was measured. Results: Patients with distant metastases showed significantly higher levels of TC, LDL-C and the LDL-C/HDL-C ratio than patients without metastases (p< 0.05). The presence of metastases was positively associated with TC, LDL-C and the LDL-C/HDL-C ratio, being independent of sex, age and BMI. Conclusions: Elevated serum lipid levels may facilitate the development of distant metastasis in CRC patients.

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“…This was seemingly due to the fact that 80% more protein is available in zymosan as apoHDL than as intact HDL. In this regard, as compared to intact LDL, intact HDL 3 has relatively more protein and is more efficient in stimulating erythrocyte phagocytosis through the Fc receptor (18).…”

mentioning

confidence: 99%

Zymosan phagocytosis by mouse peritoneal macrophages is increased by apoHDL- and not by intact HDL-covered particles

Carvalho

Tobias

Vendrame

et al. 2000

Braz J Med Biol Res

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The uptake of lipids and lipoprotein particles by macrophages undergoes phagocytic activation and the formation of foam cells are key events in atherosclerosis. In this study we determined how intact high density lipoproteins (HDL) and apolipoproteins-HDL (removal of the lipid component from HDL, i.e., apoHDL) influence the phagocytosis of zymosan by mouse peritoneal macrophages. Zymosan particles preincubated together with lipoproteins or alone (control) were incubated with the macrophages. Phagocytosis activity was reported as the percent of macrophages that internalized three or more zymosan particles. HDL co-incubated with zymosan did not influence the overall uptake of zymosan particles compared to apoHDL, which greatly enhanced the ability of the particle to be phagocytized (P<0.001). Part of this effect might be related to a greater binding of apoHDL to the particles compared to that of HDL (P<0.05). We conclude that this can be a useful method to study the ability of lipoproteins, including modified lipoproteins obtained from subjects with genetic forms of hyperlipidemia, to opsonize particles such as red blood cells and thus to investigate the processes that control the formation of foam cells and the mechanisms of atherogenesis.

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Identification of low density lipoprotein as a regulator of Fc receptor-mediated phagocytosis.

Abstract: Optimal expression of the high-affinity Fc receptor for IgG (FcRI)

Cited by 22 publications

References 29 publications

Tumor Necrosis Factor-α Promotes Macrophage-Induced Vascular Smooth Muscle Cell Apoptosis by Direct and Autocrine Mechanisms

Tumor Necrosis Factor-α Promotes Macrophage-Induced Vascular Smooth Muscle Cell Apoptosis by Direct and Autocrine Mechanisms

Serum Lipid Profile in Colorectal Cancer Patients with and without Synchronous Distant Metastases

Zymosan phagocytosis by mouse peritoneal macrophages is increased by apoHDL- and not by intact HDL-covered particles

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