Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects.

Nozaki, Satoshi; Kashiwagi, Hirokazu; Yamashita, Shizuya; Nakagawa, Tsutomu; Kostner, B; Tomiyama, Yoshiaki; Nakata, Atsuyuki; Ishigami, Masato; Miyagawa, Jun Ichiro; Kameda‐Takemura, Kaoru

doi:10.1172/jci118231

Cited by 305 publications

(209 citation statements)

References 39 publications

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“…dized LDL and accumulated less sterol than did control patients (19). Recent studies with CD36 null mice have confirmed the initial human findings and demonstrated that the presence of CD36 in macrophages promotes the accumulation of sterol and the formation of atherosclerotic lesions (16,17).…”

mentioning

confidence: 58%

HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages

Dressman¹,

Kincer²,

Матвеев³

et al. 2003

J. Clin. Invest.

135

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Protease inhibitors decrease the viral load in HIV patients, however the patients develop hypertriglyceridemia, hypercholesterolemia, and atherosclerosis. It has been assumed that protease inhibitor–dependent increases in atherosclerosis are secondary to the dyslipidemia. Incubation of THP-1 cells or human PBMCs with protease inhibitors caused upregulation of CD36 and the accumulation of cholesteryl esters. The use of CD36-blocking antibodies, a CD36 morpholino, and monocytes isolated from CD36 null mice demonstrated that protease inhibitor–induced increases in cholesteryl esters were dependent on CD36 upregulation. These data led to the hypothesis that protease inhibitors induce foam cell formation and consequently atherosclerosis by upregulating CD36 and cholesteryl ester accumulation independent of dyslipidemia. Studies with LDL receptor null mice demonstrated that low doses of protease inhibitors induce an increase in the level of CD36 and cholesteryl ester in peritoneal macrophages and the development of atherosclerosis without altering plasma lipids. Furthermore, the lack of CD36 protected the animals from protease inhibitor–induced atherosclerosis. Finally, ritonavir increased PPAR-γ and CD36 mRNA levels in a PKC- and PPAR-γ–dependent manner. We conclude that protease inhibitors contribute to the formation of atherosclerosis by promoting the upregulation of CD36 and the subsequent accumulation of sterol in macrophages

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mentioning

confidence: 58%

HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages

Dressman¹,

Kincer²,

Матвеев³

et al. 2003

J. Clin. Invest.

135

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“…The class B scavenger receptor type 2, CD36, is involved in the Mu response to oxidized LDL [7,27] Here, we study the effects of IL-13, another Th2 cytokine, on CD36 surface expression in human monocytes. Indeed, even though IL-4 and IL-13 share many structural characteristics, they also have important differences.…”

Section: Discussionmentioning

confidence: 99%

“…The class B scavenger receptor type 2, CD36, is involved in the Mu response to oxidized LDL [7,27] and mediates microglial and Mu responses to b-amyloid [28]. This scavenger receptor also recognizes anionic phospholipids [8], apoptotic cells [9], thrombospondin [29] and P. falciparum-infected erythrocytes [10].…”

Section: Discussionmentioning

confidence: 99%

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

et al. 2007

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The class B scavenger receptor CD36 is a component of the pattern recognition receptors on monocytes that recognizes a variety of molecules. CD36 expression in monocytes depends on exposure to soluble mediators. We demonstrate here that CD36 expression is induced in human monocytes following exposure to IL-13, a Th2 cytokine, via the peroxisome proliferator-activated receptor (PPAR)c pathway. Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The PPARc pathway was demonstrated using transfection of a PPARc expression plasmid into the murine macrophage cell line RAW264.7, expressing very low levels of PPARc, and in peritoneal macrophages from PPARc-conditional null mice. We also show that CD36 induction by IL-13 via PPARc is dependent on phospholipase A2 activation and that IL-13 induces the production of endogenous 15-deoxy-D 12,14 -prostaglandin J 2 , an endogenous PPARc ligand, and its nuclear localization in human monocytes. Finally, we demonstrate that CD36 and PPARc are involved in IL-13-mediated phagocytosis of Plasmodium falciparum-parasitized erythrocytes. These results reveal a novel role for PPARc in the alternative activation of monocytes by IL-13, suggesting that endogenous PPARc ligands, produced by phospholipase A2 activation, could contribute to the biochemical and cellular functions of CD36.Leukocyte signaling * These 2 authors contributed equally to this work. IntroductionThe innate immune system protects the host in the early phase of infection. Circulating monocytes and tissue macrophages (Mu) mediate much of this innate immune response [1]. The strategy of recognition in the innate response is mediated by the coordinated action of pathogen-associated molecular patterns and pattern recognition receptors. Scavenger receptors and mannose receptor are important pattern recognition receptors in monocytes/Mu [2,3]. The modulation of the expression of these receptors may be critical in the role of these cells in antigen processing, scavenging, and host defence against pathogens. Several members of the scavenger receptor family, including Mu class A scavenger receptors and CD36, have been identified as receptors for modified lipoproteins on Mu, and their relevance to lipid uptake has been demonstrated in vitro and in vivo [4]. The scavenger receptor CD36, an 88-kDa integral membrane protein, is a class B scavenger receptor expressed on a wide variety of cells, in particular on monocytes and monocytederived Mu [5,6]. CD36 is known as a receptor for the uptake of oxidatively modified low-density lipoprotein (LDL) [7] and is also able to bind anionic phospholipid phosphatidylserine [8]. This scavenger receptor is implicated in the clearance of apoptotic cells [9]. Recently, McGilvray and colleagues [10] described a CD36-dependent nonopsonic phagocytosis of erythrocytes containing P. falciparum, by monocytes and culture-derived Mu, and a decrease in the parasiteinduced TNF secretion by monocytes/Mu. These processes were accentuated by CD36 up-regulation by peroxisome proliferator-acti...

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“…Early studies illustrated the significant role of CD36 in binding/uptake of oxLDL based upon a genetic polymorphism in the CD36 gene identified in Japanese subjects shown to result in deficient expression of CD36 (the NAK aϪ phenotype) (11). Monocyte-derived macrophages isolated from these patients were seen to bind ϳ40% less oxLDL and accumulate ϳ40% less cholesteryl ester from oxLDL than cells derived from normal controls (12). The site of this oxLDL binding to CD36 has been identified and recently mapped to amino acids 157-171, with critical lysines at positions 164 and 166 (13)(14)(15).…”

mentioning

confidence: 99%

CD36 Binds Oxidized Low Density Lipoprotein (LDL) in a Mechanism Dependent upon Fatty Acid Binding

Jay

Chen

Paz

et al. 2015

Journal of Biological Chemistry

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Background: CD36 is expressed in many cell types and binds diverse ligands including oxidized LDL (oxLDL) and unesterified fatty acid (FA). Results: FA bind to CD36, which leads to oxLDL binding and uptake independent of CD36 disulfide bonds. Conclusion: Typical dietary FA enhance uptake of oxLDL. Significance: This study provides a possible mechanism for oxLDL binding CD36 that is dependent upon specific FA types.

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Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects.

Abstract: To clarify the physiological roles of CD36 as an oxidized low density lipoprotein (OxLDL) receptor, we analyzed the monocyte-derived macrophages from normal and two CD36-deficient subjects, since we identified the molecular abnormalities (

Cited by 305 publications

References 39 publications

HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages

HIV protease inhibitors promote atherosclerotic lesion formation independent of dyslipidemia by increasing CD36-dependent cholesteryl ester accumulation in macrophages

IL‐13 induces expression of CD36 in human monocytes through PPARγ activation

CD36 Binds Oxidized Low Density Lipoprotein (LDL) in a Mechanism Dependent upon Fatty Acid Binding

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