Scavenger Receptor Structure and Function in Health and Disease

Abstract

Scavenger receptors (SRs) are a ‘superfamily’ of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.

Aberrant bispecific antibody pharmacokinetics linked to liver sinusoidal endothelium clearance mechanism in cynomolgus monkeys

“…The numerous sinusoids of the liver are lined by an endocytically highly active endothelium, known as LSECs, which have been demonstrated to be the major elimination site for an array of physiological and pathophysiological soluble waste macromolecules. 36,37 These cells carry high-affinity endocytic receptors (scavenger receptors, SR) that efficiently mediate the uptake and subsequent degradation of a great number of soluble macromolecules. Although we demonstrated here that LSECs appear responsible for the unusually rapid clearance of several of our IgG-scFv and IgG-ECD fusion constructs, we acknowledge that additional studies are needed to generalize this as a mechanism with common threads across multiple BsAbs and formats.…”

“…It is, however, now appreciated that these SRs recognize an extremely diverse range of ligands that includes unmodified endogenous proteins and lipoproteins, as well as a number of conserved microbial structures, such as bacterial lipopolysaccharide and lipoteichoic acid. 36,37 Owing to the expanding number of cognate ligands, these scavenger receptors are considered to be a subclass of the membranebound pattern recognition receptors. 37,38 The wide range of scavenger receptor ligands suggests that epitopes generated by oxidation, charge or conformation may be involved in recognition of LSECs by SRs.…”

“…36,37 Owing to the expanding number of cognate ligands, these scavenger receptors are considered to be a subclass of the membranebound pattern recognition receptors. 37,38 The wide range of scavenger receptor ligands suggests that epitopes generated by oxidation, charge or conformation may be involved in recognition of LSECs by SRs. 37,38 To that, it has been proposed that peroxidation of endogenous proteins or lipoproteins resemble microbial structures facilitating recognition.…”

“…37,38 The wide range of scavenger receptor ligands suggests that epitopes generated by oxidation, charge or conformation may be involved in recognition of LSECs by SRs. 37,38 To that, it has been proposed that peroxidation of endogenous proteins or lipoproteins resemble microbial structures facilitating recognition. 37,38 In the context of our BsAb observations, since these structures are dynamic, it is plausible that they can assume conformations that appear 'foreign' in the absence or presence of a soluble antigen interaction, facilitating binding to SRs.…”

Gene therapy as advanced technology for the treatment of Leukemia: CAR-T therapy

“…The functional ends of the receptor behave as endodomain (Zani et al, 2015;Zhang et al, 2017) (Figure 6). …”