Recognition of lipoproteins by scavenger receptor class A members

Cheng, Chen; Zheng, Enlin; Yu, Bowen; Zhang, Ze; Wang, Yuanyuan; Liu, Yingbin; He, Yongning

doi:10.1016/j.jbc.2021.100948

Cited by 24 publications

(22 citation statements)

References 97 publications

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“…LOX-1 is an important receptor of oxLDL uptake in endothelial cells (Mango et al, 2011;Akhmedov et al, 2014;Barreto et al, 2021) but is also able to bind acLDL at comparable affinity (Kumano-Kuramochi et al, 2012). Other oxLDL-related known receptors are, e.g., the scavenger receptor CD36, the scavenger receptor class A member 1 (SCARA1), and the Gprotein-coupled receptor angiotensin II type 1 receptor (AT1) (Silverstein, 2018;Pandey et al, 2020;Cheng et al, 2021;Takahashi et al, 2021). Previously, E. bovis-infected host cells have been shown to upregulate LOX-1 gene transcription during first merogony (Taubert et al, 2010;Hamid et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Novel Insights Into Sterol Uptake and Intracellular Cholesterol Trafficking During Eimeria bovis Macromeront Formation

Silva

Velásquez

López-Osorio

et al. 2022

Front. Cell. Infect. Microbiol.

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Apicomplexan parasites are considered as defective in cholesterol synthesis. Consequently, they need to scavenge cholesterol from the host cell by either enhancing the uptake of extracellular cholesterol sources or by upregulating host cellular de-novo biosynthesis. Given that Eimeria bovis macromeront formation in bovine lymphatic endothelial host cells in vivo is a highly cholesterol-demanding process, we here examined host parasite interactions based on host cellular uptake of different low-density lipoprotein (LDL) types, i.e., of non-modified (LDL), oxidized (oxLDL), and acetylated LDL (acLDL). Furthermore, the expression of lipoprotein-oxidized receptor 1 (LOX-1), which mediates acLDL and oxLDL internalization, was monitored throughout first merogony, in vitro and ex vivo. Moreover, the effects of inhibitors blocking exogenous sterol uptake or intracellular transport were studied during E. bovis macromeront formation in vitro. Hence, E. bovis-infected primary bovine umbilical vein endothelial cells (BUVEC) were treated with inhibitors of sterol uptake (ezetimibe, poly-C, poly-I, sucrose) and of intracellular sterol transport and release from endosomes (progesterone, U18666A). As a read-out system, the size and number of macromeronts as well as merozoite I production were estimated. Overall, the internalization of all LDL modifications (LDL, oxLDL, acLDL) was observed in E. bovis-infected BUVEC but to different extents. Supplementation with oxLDL and acLDL at lower concentrations (5 and 10 µg/ml, respectively) resulted in a slight increase of both macromeront numbers and size; however, at higher concentrations (25–50 µg/ml), merozoite I production was diminished. LOX-1 expression was enhanced in E. bovis-infected BUVEC, especially toward the end of merogony. As an interesting finding, ezetimibe treatments led to a highly significant blockage of macromeront development and merozoite I production confirming the relevance of sterol uptake for intracellular parasite development. Less prominent effects were induced by non-specific inhibition of LDL internalization via sucrose, poly-I, and poly-C. In addition, blockage of cholesterol transport via progesterone and U18666A treatments resulted in significant inhibition of parasite development. Overall, current data underline the relevance of exogenous sterol uptake and intracellular cholesterol transport for adequate E. bovis macromeront development, unfolding new perspectives for novel drug targets against E. bovis.

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Section: Discussionmentioning

confidence: 99%

Novel Insights Into Sterol Uptake and Intracellular Cholesterol Trafficking During Eimeria bovis Macromeront Formation

Silva

Velásquez

López-Osorio

et al. 2022

Front. Cell. Infect. Microbiol.

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“…SR-A family comprises five members: SR-A1 (CD204), SR-A3, SR-A4, SR-A5, and SR-A6 (MARCO), which recognize a variety of ligands such as LPS, LTA and integrins. SR-A are implicated in several pathologies including atherosclerosis, infectious diseases and cancer (13,70,71). In most of studies the question about tumor-specific ligand of CD204 was not addressed experimentally.…”

Section: Class a Scavenger Receptorsmentioning

confidence: 99%

Macrophage scavenger receptors: Tumor support and tumor inhibition

et al. 2023

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Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells that constitute up to 50% of the cell mass of human tumors. TAMs interact with the components of the tumor microenvironment (TME) by using scavenger receptors (SRs), a large superfamily of multifunctional receptors that recognize, internalize and transport to the endosomal/lysosomal pathway apoptotic cells, cytokines, matrix molecules, lipid modified lipoproteins and other unwanted-self ligands. In our review, we summarized state-of-the art for the role of macrophage scavenger receptors in tumor development and their significance as cancer biomarkers. In this review we focused on functional activity of TAM-expressing SRs in animal models and in patients, and summarized the data for different human cancer types about the prognostic significance of TAM-expressed SRs. We discussed the role of SRs in the regulation of cancer cell biology, cell-cell and cell-matrix interaction in TME, immune status in TME, angiogenesis, and intratumoral metabolism. Targeting of tumor-promoting SRs can be a promising therapeutic approach in anti-cancer therapy. In our review we provide evidence for both tumor supporting and tumor inhibiting functions of scavenger receptors expressed on TAMs. We focused on the key differences in the prognostic and functional roles of SRs that are specific for cancer types. We highlighted perspectives for inhibition of tumor-promoting SRs in anti-cancer therapy.

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“…Oxidative modification of the protein part impairs LDL recognition by LDLR. Macrophages actively take up OxLDL by scavenger receptors (CD36, SR-A, and SR-B1) and lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) to remove excess OxLDL from the arterial wall [77][78][79] . OxLDL may be involved in ROS production, leading to endothelial cell damage [80] .…”

Section: Effects Of Oxidized Ldlmentioning

confidence: 99%

A novel insight into the nature of modified low-density lipoproteins and their role in atherosclerosis

2023

Vessel Plus

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Atherosclerosis plays a significant role in the development of cardiovascular diseases, the leading cause of death worldwide. Modification of low-density lipoproteins (LDLs) is a critical event in atherogenesis. Native LDL undergoes several modifications that can lead to the formation of atherogenic modified LDLs. LDL modifications change their physicochemical and biological properties. Possible modifications include changes in the lipoprotein particle's structure, size, charge, and composition. Uptake and utilization of modified LDLs are impaired in cells. Macrophages take up modified LDLs that promote forming of foam cells, one of the critical cellular components of atherosclerotic lesions. Nevertheless, the direct role of each atherogenic LDL modification in atherogenesis remains uncertain. This review highlights LDL's most critical atherogenic modifications, including oxidized, enzymemodified, non-oxidative, desialylated, glycated and carbamylated LDLs. Studying the role of each type of LDL modification will clarify the unknown elements of atherosclerosis progression and facilitate the development of effective methods for its diagnosis, treatment, and prevention.

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Recognition of lipoproteins by scavenger receptor class A members

Cited by 24 publications

References 97 publications

Novel Insights Into Sterol Uptake and Intracellular Cholesterol Trafficking During Eimeria bovis Macromeront Formation

Novel Insights Into Sterol Uptake and Intracellular Cholesterol Trafficking During Eimeria bovis Macromeront Formation

Macrophage scavenger receptors: Tumor support and tumor inhibition

A novel insight into the nature of modified low-density lipoproteins and their role in atherosclerosis

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