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Scavenger Receptors and Lipopolysaccharide
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Scavenger receptors of macrophages represent a trimeric integral membrane glycoproteins implicated in the pathogenesis of atherosclerosis (1,2), apoptosis or programmed cell death (3,4), and host defense against microbial pathogens or their toxic products (5–8). Analysis of tissue distribution has revealed the presence of scavenger receptor(s) in a variety of organs and tissues and identified tissue macrophages as the primary cells expressing scavenger receptor(s) (9). A unique property of scavenger receptor(s) is that it exhibit a broad binding specificity towards a variety of negatively charged ligands including chemically modified proteins, polyribonucleotides, and anionic polysaccharides (2,10). Since initial studies were primarily related to evaluation of the role of scavenger receptors in the pathogenesis of atherosclerosis, scavenger receptors were defined by their ability to bind modified low-density lipoproteins (LDL), e.g., acetylated LDL (Ac-LDL) and oxidized LDL (ox-LDL). Based on the ligand-binding characteristics and amino acid sequence analysis, there have been described at least three independent classes of scavenger receptors, namely class A, B, and C scavenger receptors (5,11–14).
Lipoprotein Metabolism in Pregnancy
Published in Emilio Herrera, Robert H. Knopp, Perinatal Biochemistry, 2020
Robert H. Knopp, Bartolomé Bonet, Miguel Angel Lasunción, Adela Montelongo, Emilio Herrera
Diabetes in pregnancy of the NIDDM type is associated with hypertriglyceridemia88,107 and a low HDL-C107 as is preeclampsia.42 Type I diabetics have little change in lipoproteins except for a reduction in HDL3 which could diminish reverse cholesterol transport, augment cholesterol transport to the fetus and promote infant macrosomia.108 As noted above, experimental diabetes does not appear to alter placental LPL activity.32,76 However, diabetes may enhance oxidative stress on lipoproteins which, in susceptible individuals, could activate uptake of oxidized or modified lipoproteins by placental macrophages via the scavenger receptor.109 Very recently, Bonet has found evidence for the scavenger receptor in immunochemically characterized cultured human placental trophoblast cells as well,109 in keeping with the results of Rebourcet et al., who have found scavenger receptor activity in placental microvilli membranes110 and cultured placental cells.111 This group has also found evidence for chemically modified LDL in placental blood.112 These findings may have great pathophysiological significance in diabetic pregnancy.
Cardiovascular Disease and Oxidative Stress
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marco Fernandes, Alisha Patel, Holger Husi
Consecutive monocyte differentiation into macrophages and their local accumulation in the adipose tissue is recognized as a key event in insulin resistance (IR) (Patsouris et al., 2014). The local deposition of insulin resistant macrophages up-regulates the scavenger receptor class B member 1 (SCARB1), which promotes foam cell formation and then the establishment of an atherosclerotic lesion (Chistiakov et al., 2017). In case of activation of the peroxisome proliferator-activated receptor gamma (PPARG), the latter described processes can be overturned by transcriptionally regulation of the macrophage insulin signalling activation (Chawla, 2010) (Fig. 7.1). ROS accumulation enduring IR and long-term hyperglycaemia adds-up to both cardiac and structural defects such as endothelial dysfunction and tissue remodelling.
Scavenger Receptor A1 Signaling Pathways Affecting Macrophage Functions in Innate and Adaptive Immunity
Published in Immunological Investigations, 2022
Elizabeth Linares-Alcántara, Fela Mendlovic
In 1979, Goldstein and Brown first discovered receptors in macrophages that recognize and degrade acetylated low-density lipoproteins (AcLDL) and oxidized LDL (OxLDL) but not native LDL, as well as polyanionic ligands (Brown and Goldstein 1983; Goldstein et al. 1979). Soon, other modified LDL receptors with broad-binding specificities were identified (Acton et al. 1994; Adachi et al. 1997; Calvo and Vega 1993; Endemann et al. 1993; Ramprasad et al. 1996; Yoshimoto et al. 2011). The term “Scavenger Receptors” (SR) was coined by Fogelmann and colleagues in 1981 and M. Krieger proposed to divide these receptors into classes and each class into types based on sequence variations (Fogelman et al. 1981; Krieger 1997). Members of each class share primary sequence homologies, while there are few or no similarities among classes of SR. In 2017, a consensus was reached concerning a standardized nomenclature for SR and classification in 12 classes (A-L, class C is only found in Drosophila melanogaster) (PrabhuDas et al. 2017). Class A1 SR (SR-A1) exists in three forms, SR-A1, SR-A1.1, and SR-A1.2 according to the more recent consensus nomenclature (PrabhuDas et al. 2017) and represents differentially spliced variants of the macrophage scavenger receptor 1 (MSR1) gene, which contains 11 exons and is located on chromosome 8 of humans and mice (Krieger 1992). Additional Class A SRs are SR-A3, SR-A4, SR-A5, and SR-A6 or MARCO.
Application of physiologically based pharmacokinetic models for therapeutic proteins and other novel modalities
Published in Xenobiotica, 2022
Rachel H. Rose, Armin Sepp, Felix Stader, Katherine L. Gill, Cong Liu, Iain Gardner
Typical ASO affinity for serum albumin in the region of Kd = 10–30 µM implies about 1–5% free fraction in circulation (Agarwal et al. 2021). Like plasma proteins, OT can be expected to enter cells non-specifically by micropinocytosis, but preferential accumulation in liver and kidneys suggests substantial contributions from additional pathways in these two organs. In the case of kidneys, renal filtration is likely to be significant for the free fraction, while in the case of liver, receptor-mediated uptake by Stabilin-1 and -2 scavengers has been implicated (Miller et al. 2016). There are many scavenger receptors expressed throughout the body, most of them poorly characterised for affinity or abundance where they recognise and remove from circulation molecules or particles with repeating structural features (Chaudhuri 1997; Miyatake et al. 2019).
Scavenger receptor A in immunity and autoimmune diseases: Compelling evidence for targeted therapy
Published in Expert Opinion on Therapeutic Targets, 2022
Yang Xie, Yuan Jia, Zhanguo Li, Fanlei Hu
The scavenger receptors (SR) were initially defined by Brown and Goldstein in 1979 [1,2] and have subsequently been divided into 10 classes (A-J) based on their structural characteristics and sequence alignments. It is now appreciated that a diverse spectrum of ligands recognized by scavenger receptors includes host-derived endogenous proteins and a number of microbial pathogens [3–5]. Therefore, scavenger receptors are considered to be a critical subclass of the pattern recognition receptors (PRRs). Similar to other PRRs, scavenger receptors play a critical role in innate immunity such as adhesion, phagocytosis, and host defense [6]. Moreover, scavenger receptors have been reported to maintain homeostasis [5] and regulate tumor progression [7]. In 1979, Brown and Goldstein also demonstrated the ability of scavenger receptors to uptake the low-density lipoprotein (LDL) [1,2], and emerging studies showed their proatherogenic function in atherosclerosis. Besides cardiovascular diseases, due to their ability to recognize such a diverse repertoire of ligands, there is increasing evidence indicating the involvement of scavenger receptors in the pathogenesis of multiple diseases, such as Alzheimer’s disease, type 2 diabetes, autoimmune diseases, and cancer [7,8].