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Sci. Signal., 26 May 2009
Vol. 2, Issue 72, p. re3
[DOI: 10.1126/scisignal.272re3]


CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior

Roy L. Silverstein* and Maria Febbraio

Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation and Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44195, USA.

Gloss: CD36 is a multifunctional cell-surface receptor present on many cell types, including platelets, mononuclear phagocytes, and muscle, fat, and gut cells. It is conserved in mammals, and there are many invertebrate orthologs. CD36 binds to several major classes of ligands, including the matrix protein thrombospondin, long-chain fatty acids, and oxidized phospholipids and lipoproteins; in different contexts, it serves to regulate angiogenesis, innate immune responses, fatty acid metabolism, and sensory responses to fatty acids. CD36 signaling is mediated by activation of specific intracellular pathways that may include kinases of the Src family and mitogen-activated protein kinases. Because of the importance of CD36 signaling in human diseases, including atherosclerosis, thrombosis, Alzheimer’s disease, obesity, diabetes, and cancer, these signaling pathways are under intense scrutiny. This Review includes two figures and 123 citations.

* Corresponding author. E-mail, silverr2{at}

Citation: R. L. Silverstein, M. Febbraio, CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior. Sci. Signal. 2, re3 (2009).

Rosiglitazone-induced CD36 up-regulation resolves inflammation by PPAR{gamma} and 5-LO-dependent pathways.
I. Ballesteros, M. I. Cuartero, J. M. Pradillo, J. de la Parra, A. Perez-Ruiz, A. Corbi, M. Ricote, J. A. Hamilton, M. Sobrado, J. Vivancos, et al. (2014)
J. Leukoc. Biol. 95, 587-598
   Abstract »    Full Text »    PDF »
Skeletal muscle as a target of LXR agonist after long-term treatment: focus on lipid homeostasis.
A. Archer, J. Laurencikiene, O. Ahmed, K. R. Steffensen, P. Parini, J.-A. Gustafsson, and M. Korach-Andre (2014)
Am J Physiol Endocrinol Metab 306, E494-E502
   Abstract »    Full Text »    PDF »
Peripheral venous congestion causes inflammation, neurohormonal, and endothelial cell activation.
P. C. Colombo, D. Onat, A. Harxhi, R. T. Demmer, Y. Hayashi, S. Jelic, T. H. LeJemtel, L. Bucciarelli, M. Kebschull, P. Papapanou, et al. (2014)
Eur. Heart J. 35, 448-454
   Abstract »    Full Text »    PDF »
CD36-deficient mice are resistant to alcohol- and high-carbohydrate-induced hepatic steatosis.
R. D. Clugston, J. J. Yuen, Y. Hu, N. A. Abumrad, P. D. Berk, I. J. Goldberg, W. S. Blaner, and L.-S. Huang (2014)
J. Lipid Res. 55, 239-246
   Abstract »    Full Text »    PDF »
Thrombospondin-1/CD36 pathway contributes to bone marrow-derived angiogenic cell dysfunction in type 1 diabetes via Sonic hedgehog pathway suppression.
J.-M. Wang, J. S. Isenberg, T. R. Billiar, and A. F. Chen (2013)
Am J Physiol Endocrinol Metab 305, E1464-E1472
   Abstract »    Full Text »    PDF »
The class A scavenger receptor SR-A/CD204 and the class B scavenger receptor CD36 regulate immune functions of macrophages differently.
S. Jozefowski, R. Biedron, M. Srottek, M. Chadzinska, and J. Marcinkiewicz (2013)
Innate Immunity
   Abstract »    Full Text »    PDF »
Thrombospondin-1 modulates VEGF signaling via CD36 by recruiting SHP-1 to VEGFR2 complex in microvascular endothelial cells.
L.-Y. Chu, D. P. Ramakrishnan, and R. L. Silverstein (2013)
Blood 122, 1822-1832
   Abstract »    Full Text »    PDF »
PP2 and piceatannol inhibit PrP106-126-induced iNOS activation mediated by CD36 in BV2 microglia.
S. Zhang, L. Yang, M. Kouadir, R. Tan, Y. Lu, J. Chang, B. Xu, X. Yin, X. Zhou, and D. Zhao (2013)
Acta Biochim Biophys Sin 45, 763-772
   Abstract »    Full Text »    PDF »
Vav Guanine Nucleotide Exchange Factors Regulate Atherosclerotic Lesion Development in Mice.
S. O. Rahaman, W. Li, and R. L. Silverstein (2013)
Arterioscler Thromb Vasc Biol 33, 2053-2057
   Abstract »    Full Text »    PDF »
CD36 Mediates Endothelial Dysfunction Downstream of Circulating Factors Induced by O3 Exposure.
S. Robertson, E. S. Colombo, S. N. Lucas, P. R. Hall, M. Febbraio, M. L. Paffett, and M. J. Campen (2013)
Toxicol. Sci. 134, 304-311
   Abstract »    Full Text »    PDF »
Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation.
P. Kong, C. Gonzalez-Quesada, N. Li, M. Cavalera, D.-W. Lee, and N. G. Frangogiannis (2013)
Am J Physiol Endocrinol Metab 305, E439-E450
   Abstract »    Full Text »    PDF »
The involvement of CD36 in monocyte activation by antiphospholipid antibodies.
M. Kato, T. Atsumi, K. Oku, O. Amengual, H. Nakagawa, Y. Fujieda, K. Otomo, T. Horita, S. Yasuda, and T. Koike (2013)
Lupus 22, 761-771
   Abstract »    Full Text »    PDF »
Shedding Light on Impaired Efferocytosis and Nonresolving Inflammation.
M. L. Novak and E. B. Thorp (2013)
Circ. Res. 113, 9-12
   Full Text »    PDF »
Macrophage ADAM17 Deficiency Augments CD36-Dependent Apoptotic Cell Uptake and the Linked Anti-Inflammatory Phenotype.
W. S. Driscoll, T. Vaisar, J. Tang, C. L. Wilson, and E. W. Raines (2013)
Circ. Res. 113, 52-61
   Abstract »    Full Text »    PDF »
The Scavenger Receptor CD36 Downmodulates the Early Inflammatory Response while Enhancing Bacterial Phagocytosis during Pneumococcal Pneumonia.
O. Sharif, U. Matt, S. Saluzzo, K. Lakovits, I. Haslinger, T. Furtner, B. Doninger, and S. Knapp (2013)
J. Immunol. 190, 5640-5648
   Abstract »    Full Text »    PDF »
AICAR inhibits PPAR{gamma} during monocyte differentiation to attenuate inflammatory responses to atherogenic lipids.
D. Namgaladze, M. Kemmerer, A. von Knethen, and B. Brune (2013)
Cardiovasc Res 98, 479-487
   Abstract »    Full Text »    PDF »
Sulfo-N-succinimidyl Oleate (SSO) Inhibits Fatty Acid Uptake and Signaling for Intracellular Calcium via Binding CD36 Lysine 164: SSO ALSO INHIBITS OXIDIZED LOW DENSITY LIPOPROTEIN UPTAKE BY MACROPHAGES.
O. Kuda, T. A. Pietka, Z. Demianova, E. Kudova, J. Cvacka, J. Kopecky, and N. A. Abumrad (2013)
J. Biol. Chem. 288, 15547-15555
   Abstract »    Full Text »    PDF »
Selenoprotein K is required for palmitoylation of CD36 in macrophages: implications in foam cell formation and atherogenesis.
S. Meiler, Y. Baumer, Z. Huang, F. W. Hoffmann, G. J. Fredericks, A. H. Rose, R. L. Norton, P. R. Hoffmann, and W. A. Boisvert (2013)
J. Leukoc. Biol. 93, 771-780
   Abstract »    Full Text »    PDF »
Endothelial Fatty Acid Transport: Role of Vascular Endothelial Growth Factor B.
C. Hagberg, A. Mehlem, A. Falkevall, L. Muhl, and U. Eriksson (2013)
Physiology 28, 125-134
   Abstract »    Full Text »    PDF »
Innate immunity receptor CD36 promotes cerebral amyloid angiopathy.
L. Park, J. Zhou, P. Zhou, R. Pistick, S. El Jamal, L. Younkin, J. Pierce, A. Arreguin, J. Anrather, S. G. Younkin, et al. (2013)
PNAS 110, 3089-3094
   Abstract »    Full Text »    PDF »
CD36 homolog divergence is responsible for the selectivity of carotenoid species migration to the silk gland of the silkworm Bombyx mori.
T. Sakudoh, S. Kuwazaki, T. Iizuka, J. Narukawa, K. Yamamoto, K. Uchino, H. Sezutsu, Y. Banno, and K. Tsuchida (2013)
J. Lipid Res. 54, 482-495
   Abstract »    Full Text »    PDF »
From Macrophage Interleukin-13 Receptor to Foam Cell Formation: MECHANISMS FOR {alpha}M{beta}2 INTEGRIN INTERFERENCE.
V. P. Yakubenko, L. C. Hsi, M. K. Cathcart, and A. Bhattacharjee (2013)
J. Biol. Chem. 288, 2778-2788
   Abstract »    Full Text »    PDF »
Brain and Circulating Levels of A{beta}1-40 Differentially Contribute to Vasomotor Dysfunction in the Mouse Brain.
L. Park, P. Zhou, K. Koizumi, S. El Jamal, M. L. Previti, W. E. Van Nostrand, G. Carlson, and C. Iadecola (2013)
Stroke 44, 198-204
   Abstract »    Full Text »    PDF »
CD36 and Na/K-ATPase-{alpha}1 Form a Proinflammatory Signaling Loop in Kidney.
D. J. Kennedy, Y. Chen, W. Huang, J. Viterna, J. Liu, K. Westfall, J. Tian, D. J. Bartlett, W. H. W. Tang, Z. Xie, et al. (2013)
Hypertension 61, 216-224
   Abstract »    Full Text »    PDF »
CD36 level and trafficking are determinants of lipolysis in adipocytes.
D. Zhou, D. Samovski, A. L. Okunade, P. D. Stahl, N. A. Abumrad, and X. Su (2012)
FASEB J 26, 4733-4742
   Abstract »    Full Text »    PDF »
EP 80317, a selective CD36 ligand, shows cardioprotective effects against post-ischaemic myocardial damage in mice.
V. L. Bessi, S. M. Labbe, D. N. Huynh, L. Menard, C. Jossart, M. Febbraio, B. Guerin, M. Bentourkia, R. Lecomte, A. C. Carpentier, et al. (2012)
Cardiovasc Res 96, 99-108
   Abstract »    Full Text »    PDF »
CD36 Repression Activates a Multicellular Stromal Program Shared by High Mammographic Density and Tumor Tissues.
R. A. DeFilippis, H. Chang, N. Dumont, J. T. Rabban, Y.-Y. Chen, G. V. Fontenay, H. K. Berman, M. L. Gauthier, J. Zhao, D. Hu, et al. (2012)
Cancer Discovery 2, 826-839
   Abstract »    Full Text »    PDF »
High insulin levels are required for FAT/CD36 plasma membrane translocation and enhanced fatty acid uptake in obese Zucker rat hepatocytes.
X. Buque, A. Cano, M. E. Miquilena-Colina, C. Garcia-Monzon, B. Ochoa, and P. Aspichueta (2012)
Am J Physiol Endocrinol Metab 303, E504-E514
   Abstract »    Full Text »    PDF »
Oxidatively Modified Low Density Lipoprotein (LDL) Inhibits TLR2 and TLR4 Cytokine Responses in Human Monocytes but Not in Macrophages.
Y. Kannan, K. Sundaram, C. Aluganti Narasimhulu, S. Parthasarathy, and M. D. Wewers (2012)
J. Biol. Chem. 287, 23479-23488
   Abstract »    Full Text »    PDF »
Role of the Gut in Lipid Homeostasis.
N. A. Abumrad and N. O. Davidson (2012)
Physiol Rev 92, 1061-1085
   Abstract »    Full Text »    PDF »
CD36 Ectodomain Phosphorylation Blocks Thrombospondin-1 Binding: Structure-Function Relationships and Regulation by Protein Kinase C.
L.-Y. Chu and R. L. Silverstein (2012)
Arterioscler Thromb Vasc Biol 32, 760-767
   Abstract »    Full Text »    PDF »
Reduced CD36-dependent tissue sequestration of Plasmodium-infected erythrocytes is detrimental to malaria parasite growth in vivo.
J. Fonager, E. M. Pasini, J. A. M. Braks, O. Klop, J. Ramesar, E. J. Remarque, I. O. C. M. Vroegrijk, S. G. van Duinen, A. W. Thomas, S. M. Khan, et al. (2012)
J. Exp. Med. 209, 93-107
   Abstract »    Full Text »    PDF »
Gene Expression in Livers of BALB/C and C57BL/6J Mice Fed a High-Fat Diet.
S. Nishikawa, J. Sugimoto, M. Okada, T. Sakairi, and S. Takagi (2012)
Toxicol Pathol 40, 71-82
   Abstract »    Full Text »    PDF »
Clinical significance of serum levels of sCD36 in patients with systemic sclerosis: preliminary data.
I. H. Bassyouni, T. A. Gheita, and R. M. Talaat (2011)
Rheumatology 50, 2108-2112
   Abstract »    Full Text »    PDF »
Luminal Lipid Regulates CD36 Levels and Downstream Signaling to Stimulate Chylomicron Synthesis.
T. T. T. Tran, H. Poirier, L. Clement, F. Nassir, M. M. A. L. Pelsers, V. Petit, P. Degrace, M.-C. Monnot, J. F. C. Glatz, N. A. Abumrad, et al. (2011)
J. Biol. Chem. 286, 25201-25210
   Abstract »    Full Text »    PDF »
Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms.
A. Ghosh, G. Murugesan, K. Chen, L. Zhang, Q. Wang, M. Febbraio, R. M. Anselmo, K. Marchant, J. Barnard, and R. L. Silverstein (2011)
Blood 117, 6355-6366
   Abstract »    Full Text »    PDF »
Lysophosphatidic acid suppresses endothelial cell CD36 expression and promotes angiogenesis via a PKD-1-dependent signaling pathway.
B. Ren, J. Hale, S. Srikanthan, and R. L. Silverstein (2011)
Blood 117, 6036-6045
   Abstract »    Full Text »    PDF »
C. J. Lowenstein (2011)
Blood 117, 5557-5559
   Full Text »    PDF »
CD36 Protein Is Involved in Store-operated Calcium Flux, Phospholipase A2 Activation, and Production of Prostaglandin E2.
O. Kuda, C. M. Jenkins, J. R. Skinner, S. H. Moon, X. Su, R. W. Gross, and N. A. Abumrad (2011)
J. Biol. Chem. 286, 17785-17795
   Abstract »    Full Text »    PDF »
Hematopoietic Cell-Restricted Deletion of CD36 Reduces High-Fat Diet-Induced Macrophage Infiltration and Improves Insulin Signaling in Adipose Tissue.
H. T. Nicholls, G. Kowalski, D. J. Kennedy, S. Risis, L. A. Zaffino, N. Watson, P. Kanellakis, M. J. Watt, A. Bobik, A. Bonen, et al. (2011)
Diabetes 60, 1100-1110
   Abstract »    Full Text »    PDF »
Vav Family Rho Guanine Nucleotide Exchange Factors Regulate CD36-mediated Macrophage Foam Cell Formation.
S. O. Rahaman, W. Swat, M. Febbraio, and R. L. Silverstein (2011)
J. Biol. Chem. 286, 7010-7017
   Abstract »    Full Text »    PDF »
αM{beta}2 Integrin Activation Prevents Alternative Activation of Human and Murine Macrophages and Impedes Foam Cell Formation.
V. P. Yakubenko, A. Bhattacharjee, E. Pluskota, and M. K. Cathcart (2011)
Circ. Res. 108, 544-554
   Abstract »    Full Text »    PDF »
Polymorphisms in the CD36/FAT gene are associated with plasma vitamin E concentrations in humans.
S. Lecompte, F. Szabo de Edelenyi, L. Goumidi, G. Maiani, G. Moschonis, K. Widhalm, D. Molnar, A. Kafatos, A. Spinneker, C. Breidenassel, et al. (2011)
Am J Clin Nutr 93, 644-651
   Abstract »    Full Text »    PDF »
CD36: the common soil for inflammation in obesity and atherosclerosis?.
Z. Yang and X.-F. Ming (2011)
Cardiovasc Res 89, 485-486
   Full Text »    PDF »
Brain angiogenesis inhibitor 1 (BAI1) is a pattern recognition receptor that mediates macrophage binding and engulfment of Gram-negative bacteria.
S. Das, K. A. Owen, K. T. Ly, D. Park, S. G. Black, J. M. Wilson, C. D. Sifri, K. S. Ravichandran, P. B. Ernst, and J. E. Casanova (2011)
PNAS 108, 2136-2141
   Abstract »    Full Text »    PDF »
Common CD36 SNPs reduce protein expression and may contribute to a protective atherogenic profile.
L. Love-Gregory, R. Sherva, T. Schappe, J.-S. Qi, J. McCrea, S. Klein, M. A. Connelly, and N. A. Abumrad (2011)
Hum. Mol. Genet. 20, 193-201
   Abstract »    Full Text »    PDF »
Nuclear Orphan Receptor TAK1/TR4-Deficient Mice Are Protected Against Obesity-Linked Inflammation, Hepatic Steatosis, and Insulin Resistance.
H. S. Kang, K. Okamoto, Y.-S. Kim, Y. Takeda, C. D. Bortner, H. Dang, T. Wada, W. Xie, X.-P. Yang, G. Liao, et al. (2011)
Diabetes 60, 177-188
   Abstract »    Full Text »    PDF »
The Evolution of Extracellular Matrix.
S. Ozbek, P. G. Balasubramanian, R. Chiquet-Ehrismann, R. P. Tucker, and J. C. Adams (2010)
Mol. Biol. Cell 21, 4300-4305
   Abstract »    Full Text »    PDF »
Oxidized Low-Density Lipoprotein and Atherosclerosis.
D. Steinberg and J. L. Witztum (2010)
Arterioscler Thromb Vasc Biol 30, 2311-2316
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Regulation of Platelet Function by Class B Scavenger Receptors in Hyperlipidemia.
A. Zimman and E. A. Podrez (2010)
Arterioscler Thromb Vasc Biol 30, 2350-2356
   Abstract »    Full Text »    PDF »
Tlr2 is critical for diet-induced metabolic syndrome in a murine model.
R. W. Himes and C. W. Smith (2010)
FASEB J 24, 731-739
   Abstract »    Full Text »    PDF »
Disease-causing mutations within the lysosomal integral membrane protein type 2 (LIMP-2) reveal the nature of binding to its ligand {beta}-glucocerebrosidase.
J. Blanz, J. Groth, C. Zachos, C. Wehling, P. Saftig, and M. Schwake (2010)
Hum. Mol. Genet. 19, 563-572
   Abstract »    Full Text »    PDF »

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