Mechanisms of cell signaling by the scavenger receptor CD36: Implications in atherosclerosis and thrombosis

Department of Cell Biology, Lerner Research Institute, NC10, Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195, USA.
Transactions of the American Clinical and Climatological Association 01/2010; 121:206-20.
Source: PubMed


CD36 is a multifunctional membrane receptor present on mononuclear phagocytes, platelets, and other cells that serves as a scavenger receptor for oxidized phospholipids, apoptotic cells and certain microbial pathogens. On macrophages, CD36 interaction with oxidized LDL (oxLDL) triggers a signaling response that is pro-inflammatory and pro-atherogenic. The signaling pathway involves activation of src-family kinases, MAP kinases, and Vav family guanine nucleotide exchange factors and results in ligand internalization, foam cell formation and inhibition of migration. On platelets, CD36 interaction with oxLDL and cell-derived microparticles transduces intracellular signals that render them more reactive to low concentrations of classical agonists. In vitro studies and in vivo experiments in CD36 null mice have revealed an important mechanistic role for CD36 in atherosclerosis and thrombosis. Identification of the precise CD36 signaling pathways in specific cells elicited in response to specific ligands may yield novel targets for drug development in athero-thrombotic disorders.

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    • "production of inflammatory mediators (Helming et al. 2009; Hoosdally et al. 2009). The effects of CD36 are contextdependent in injured adult brain, injurious in the experimental setting of Alzheimer's disease and adult stroke (Cho et al. 2005; Rahaman et al. 2006; Silverstein et al. 2010) but beneficial following intracerebral hemorrhage, by facilitating hematoma resolution by mediating Peroxisome proliferatoractivated receptor gamma (PPARg)-dependent phagocytosis of red blood cells by microglia (Zhao et al. 2007). We showed that genetic deletion of CD36 enhances ischemic injury in neonatal brain, in part by diminishing phagocytotic activity of microglia after acute transient middle cerebral artery occlusion (tMCAO) (Woo et al. 2012). "
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    ABSTRACT: The stage of brain development at the time of stroke has a major impact on the pathophysiological mechanisms of ischemic damage, including the neuroinflammatory response. Microglial cells have been shown to contribute to acute and sub-chronic injury in adult stroke models, whereas in neonatal rodents we showed that microglial cells serve as endogenous neuroprotectants early following transient middle cerebral artery occlusion (tMCAO), limiting neuroinflammation and injury. In the neonate, microglial depletion or lack of the scavenger receptor CD36 exacerbates injury. In this study we asked if lack of CD36 affects microglial phenotypes after neonatal stroke. Using RT-PCR we characterized the patterns of gene expression in microglia isolated from injured regions following acute tMCAO in postnatal day 10 mice and showed that expression of several pro-inflammatory genes, including Toll-like receptors (TLR), remains largely unaffected in activated microglia in injured regions. Using multiple biochemical assays we demonstrated that lack of CD36 alters several functions of microglia in acutely injured neonatal brain: it further enhances accumulation of the chemokine MCP-1, affects the number of CD11b(+) /CD45(+) cells, along with protein expression of its co-receptor, TLR2, but does not affect accumulation of superoxide in microglia or the cytokines TNFα and IL-1β in injured regions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Neurochemistry 07/2015; DOI:10.1111/jnc.13239 · 4.28 Impact Factor
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    • "As a consequence, matrix metalloproteinases, proinflammatory cytokines, and chemoattractants enhance inflammatory infiltrates and vascular remodeling [9, 10]. CD36 has a critical role in the atherosclerotic plaque development [11–14]. However, their role in cardiovascular complications of RA has not been studied. "
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    ABSTRACT: Patients with rheumatoid arthritis (RA) have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC) and carotid intima-media thickness (cIMT) in patients with RA. Methods. We included 67 patients with RA from the Rheumatology Department of Hospital Civil “Dr. Juan I. Menchaca,” Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNFα were tested. Results. We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (P < 0.001). CD36 mean fluorescence intensity had negative correlations with cIMT (r = −0.578, P < 0.001), ox-LDL (r = −0.427, P = 0.05), TNFα (r = −0.729, P < 0.001), and IL-6 (r = −0.822, P < 0.001). Conclusion. RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA.
    BioMed Research International 06/2014; 2014(Suppl 2):736786. DOI:10.1155/2014/736786 · 3.17 Impact Factor
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    • "CD36 is a membrane glycoprotein that belongs to the class B scavenger receptor family that interacts with other membrane receptors such as TLRs. This receptor plays a role during tumor growth, inflammation, wound healing, and angiogenesis and is able to recognize PAMPs or pathogen-infected cells by acting as a phagocytic receptor [78, 79]. During the host recognition of S. aureus mediated by TLR2, CD36 may act as a facilitator or coreceptor for diacylglyceride recognition through the TLR2/6 complex mediating bacterial invasion primarily in phagocytic cells [27]. "
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    ABSTRACT: Staphylococcus aureus is a successful human and animal pathogen. The majority of infections caused by this pathogen are life threatening, primarily because S. aureus has developed multiple evasion strategies, possesses intracellular persistence for long periods, and targets the skin and soft tissues. Therefore, it is very important to understand the mechanisms employed by S. aureus to colonize and proliferate in these cells. The aim of this review is to describe the recent discoveries concerning the host receptors of nonprofessional phagocytes involved in S. aureus internalization. Most of the knowledge related to the interaction of S. aureus with its host cells has been described in professional phagocytic cells such as macrophages. Here, we showed that in nonprofessional phagocytes the α 5 β 1 integrin host receptor, chaperons, and the scavenger receptor CD36 are the main receptors employed during S. aureus internalization. The characterization and identification of new bacterial effectors and the host cell receptors involved will undoubtedly lead to new discoveries with beneficial purposes.
    BioMed Research International 04/2014; 2014:538546. DOI:10.1155/2014/538546 · 3.17 Impact Factor
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