Human scavenger protein AIM increases foam cell formation and CD36-mediated oxLDL uptake

Amézaga, Núria; Sanjurjo, Lucía; Julve, Josep; Aran, Gemma; Pérez-Cabezas, Begoña; Bastos-Amador, Patricia; Armengol, Carolina; Vilella, Ramón; Escolà‐Gil, Joan Carles; Blanco‐Vaca, Francisco; Borràs, Francesc E.; Valledor, Annabel F.; Sarrias, María Rosa

doi:10.1189/jlb.1212660

Cited by 40 publications

(72 citation statements)

References 55 publications

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“…We analyzed the CD36 receptor because of previous evidence that links the activity of these 2 molecules. 24,26 Flow cytometry analysis showed that CD5L induced higher MF cell surface expression of CD36, as previously observed. 26 Interestingly, in THP1-Vector MF, silencing of CD36 alone did not alter autophagy markers, which were almost absent, suggesting that this receptor does not modulate autophagy in basal conditions.…”

Section: Discussionsupporting

confidence: 60%

“…24,26 Flow cytometry analysis showed that CD5L induced higher MF cell surface expression of CD36, as previously observed. 26 Interestingly, in THP1-Vector MF, silencing of CD36 alone did not alter autophagy markers, which were almost absent, suggesting that this receptor does not modulate autophagy in basal conditions. In contrast, the reduction in CD36 cell surface receptor availability in CD5L-expressing MF lowered CD5L-induced LC3 puncta formation and LC3-LysoTracker Red colocalization.…”

Section: Discussionsupporting

confidence: 60%

“…As mouse CD5L expression disappears in cultured cells 19,45 and neither THP1 MK nor PB monocytes express detectable levels of human CD5L protein, 26 we generated a MK cell line that stably expresses human CD5L (THP1-HsCD5L) 26 and produced a new recombinant form of this protein (r-HsCD5L) with improved yield to supplement PB monocyte cultures. We then analyzed whether THP1-HsCD5L MK transfectants and the new rHsCD5L produced and purified in our laboratory retained the potential to inhibit the TNF response to TLR stimuli in PB monocytes.…”

Section: Cd5l Inhibits Tlr-induced Tnf Mrna Synthesis and Secretionmentioning

confidence: 99%

“…26 Consequently, we next tested whether CD36 is the receptor that mediates CD5L induction of MK autophagy (Fig. 7).…”

Section: Cd5l Expression Induces Double-membrane Vesicle Formation Inmentioning

confidence: 99%

“…22 More recently, our group has demonstrated that CD5L increases MK foam cell formation and CD36-mediated oxidized low-density lipoprotein (oxLDL) uptake. 26 CD36 is an 88-kDa transmembrane glycoprotein expressed in a wide variety of cell types, such as those of the microvascular endothelium, "professional" phagocytes (including MK, dendritic cells, and microglia) and retinal pigment epithelium, erythroid precursors, hepatocytes, adipocytes, cardiac and skeletal myocytes, and specialized epithelia of the breast, kidney, and gut. 27 Accumulating evidence shows that CD36 recognizes many types of ligands, including thrombospondin, 28 Plasmodium falciparum, 29,30 bacterial cell wall components, 31 phosphatidylserine, and oxidized phosphatidylserine that are expressed on the surface of apoptotic cells, 32 and oxLDL, 33 among others.…”

Section: Introductionmentioning

confidence: 99%

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The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses

et al. 2015

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Abbreviations: 3-MA, 3-methyladenine; AKT, v-akt murine thymoma viral oncogene homolog; ALB, albumin; ATG7, autophagyrelated 7; CD, cluster of differentiation; CD5L, CD5 molecule-like; FCS, fetal calf serum; FSL1, pam2CGDPKHPKSF; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IL, interleukin; MAP1LC3A/B (LC3), microtubule-associated protein 1 light chain 3 a/b; LPS, lipopolysaccharide; LTA, lipoteichoic acid; MK, macrophages; MAPK, mitogen-activated protein kinase; moAb, monoclonal antibody;; NFKB, nuclear factor of kappa light polypeptide gene enhancer in B-cells; oxLDL, oxidized low-density lipoprotein; PB monocytes, peripheral blood monocytes; PBS, phosphate-buffered saline; PI3K, phosphoinositide 3-kinase; PIK3C3, phosphatidylinositol 3-kinase, catalytic subunit type 3; poAb, polyclonal antibody; PMA, phorbol 12-myristate 13-acetate; PtdIns3K, phosphatidylinositol 3-kinase; PtdIns3P, phosphatidylinositol 3-phosphate; r-HsCD5L, recombinant human (Homo sapiens) CD5L; RELA, v-rel avian reticuloendotheliosis viral oncogene homolog A; siRNA, short interference RNA; SRCR, scavenger receptor cysteine-rich; TBS, tris-buffered saline; TLRs, toll-like receptors; TNF, tumor necrosis factor.CD5L (CD5 molecule-like) is a secreted glycoprotein that participates in host response to bacterial infection. CD5L influences the monocyte inflammatory response to the bacterial surface molecules lipopolysaccharide (LPS) and lipoteichoic acid (LTA) by inhibiting TNF secretion. Here we studied the intracellular events that lead to macrophage TNF inhibition by human CD5L. To accomplish this goal, we performed functional analyses with human monocytic THP1 macrophages, as well as with peripheral blood monocytes. Inhibition of phosphatidylinositol 3-kinase (PtdIns3K) reversed the inhibitory effect of CD5L on TNF secretion. Among the various PtdIns3K isoforms, our results indicated that CD5L activates PtdIns3K (whose catalytic subunit is termed PIK3C3), a key modulator involved in autophagy. Further analysis revealed a concomitant enhancement of autophagy markers such as cellular LC3-II content, increased LC3 puncta, as well as LC3-LysoTracker Red colocalization. Moreover, electron microscopy showed an increased presence of cytosolic autophagosomes in THP1 macrophages overexpressing CD5L. Besides preventing TNF secretion, CD5L also inhibited IL1B and enhanced IL10 secretion. This macrophage anti-inflammatory pattern of CD5L was reverted upon silencing of autophagy protein ATG7 by siRNA transfection. Additional siRNA experiments in THP1 macrophages indicated that the induction of autophagy mechanisms by CD5L was achieved through cell-surface scavenger receptor CD36, a multiligand receptor expressed in a wide variety of cell types. Our data represent the first evidence that CD36 is involved in autophagy and point to a significant contribution of the CD5L-CD36 axis to the induction of macrophage autophagy.

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Section: Discussionsupporting

confidence: 60%

Section: Discussionsupporting

confidence: 60%

Section: Cd5l Inhibits Tlr-induced Tnf Mrna Synthesis and Secretionmentioning

confidence: 99%

“…26 Consequently, we next tested whether CD36 is the receptor that mediates CD5L induction of MK autophagy (Fig. 7).…”

Section: Cd5l Expression Induces Double-membrane Vesicle Formation Inmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses

et al. 2015

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Macrophage Foam Cells

Valledor

Lloberas

2015

Encyclopedia of Life Sciences

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Foam cells are lipid‐loaded macrophages that are generated from the massive uptake of modified low‐density lipoproteins and the intracytoplasmatic accumulation of cholesteryl esters. Foam cells are present in all stages of atherosclerosis and participate in inflammatory responses and tissue remodelling within the arterial intima. Foam cells can also be generated as a consequence of infection by persistent pathogens, such as Mycobacterium , Chlamydia and Toxoplasma . These pathogens meet nutritional advantages by residing within cells that accumulate lipids. When the immune system is unable to eliminate substances perceived as foreign, it produces a granuloma, composed mostly of macrophages, attempting to wall off the non‐self material. This article reviews the processes that lead to the regulation of foam cell formation in atherosclerosis and infection. Key Concepts Foam cells are lipid‐loaded macrophages. Foam cells are generated upon massive uptake of modified low‐density lipoproteins and the intracellular accumulation of cholesteryl esters. Foam cells form during development of atherosclerosis and as a result of different infections. Foam cells participate in inflammatory responses and tissue remodelling. Endothelial transmigration of monocytes is the first step in the development of atherosclerosis. Once monocytes reach the arterial wall intima, they undergo phenotypic transformation into macrophages, internalise large amounts of modified LDLs and become foam cells. Heterodimers of liver X receptors (LXR) and retinoid X receptors (RXR) directly upregulate the expression of several genes involved in lipid and lipoprotein homeostasis. When the immune system is unable to eliminate substances perceived as foreign, it produces a granuloma, composed mostly of macrophages, that attempts to wall off the non‐self material.

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Multiplexed LC–ESI–MRM‐MS‐based Assay for Identification of Coronary Artery Disease Biomarkers in Human Plasma

Anwar¹,

Dai

Wilson-McManus

et al. 2019

Proteomics Clinical Apps

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Purpose: A highly-multiplexed LC-ESI-multiple reaction monitoring-MSbased assay is developed for the identification of coronary artery disease (CAD) biomarkers in human plasma. Experimental design: The assay is used to measure 107 stable isotope labeled peptide standards and native peptides from 64 putative biomarkers of cardiovascular diseases in tryptic digests of plasma from subjects with (n = 70) and without (n = 45) angiographic evidence of CAD and no subsequent cardiovascular mortality during follow-up. Results: Extensive computational and statistical analysis reveals six plasma proteins associated with CAD, namely apolipoprotein CII, C reactive protein, CD5 antigen-like, fibronectin, inter alpha trypsin inhibitor heavy chain H1, and protein S. The identified proteins are combined into a LASSO-logistic score with high classification performance (cross-validated area under the curve = 0.74). When combined with a separate score computed from markers currently used in the clinic with similar performance, the area under the receiver operating curve increases to 0.84. Similar results are observed in an independent set of subjects (n = 87). Conclusions and clinical relevance: If externally validated, the assay and identified biomarkers can improve CAD risk stratification.

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Human scavenger protein AIM increases foam cell formation and CD36-mediated oxLDL uptake

Cited by 40 publications

References 55 publications

The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses

The human CD5L/AIM-CD36 axis: A novel autophagy inducer in macrophages that modulates inflammatory responses

Macrophage Foam Cells

Multiplexed LC–ESI–MRM‐MS‐based Assay for Identification of Coronary Artery Disease Biomarkers in Human Plasma

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