The Class A Scavenger Receptor Binds to Proteoglycans and Mediates Adhesion of Macrophages to the Extracellular Matrix

Santiago‐García, Juan; Kodama, Tatsuhiko; Pitas, Robert E.

doi:10.1074/jbc.m208358200

Cited by 90 publications

(69 citation statements)

References 38 publications

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“…Also, scavenger receptors have functions beyond the uptake of oxidized LDL (203b). For example, the scavenger receptor A also plays an important role in the adhesion of macrophages to extracellular matrix (799) and cells, thereby participating in "proinflammatory" action providing for the recruitment of mononuclear phagocytes to and their retention in ligand-rich tissues such as in atherosclerotic lesion (256). In addition, and similar to the situation with antioxidant intervention studies, not all results from atherosclerosis experiments are in agreement (203b).…”

Section: Ldl Oxidation Versus Atherosclerosissupporting

confidence: 74%

Role of Oxidative Modifications in Atherosclerosis

Stocker¹,

Keaney²

2004

Physiological Reviews

2,258

1,756

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This review focuses on the role of oxidative processes in atherosclerosis and its resultant cardiovascular events. There is now a consensus that atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. The oxidative modification hypothesis of atherosclerosis predicts that low-density lipoprotein (LDL) oxidation is an early event in atherosclerosis and that oxidized LDL contributes to atherogenesis. In support of this hypothesis, oxidized LDL can support foam cell formation in vitro, the lipid in human lesions is substantially oxidized, there is evidence for the presence of oxidized LDL in vivo, oxidized LDL has a number of potentially proatherogenic activities, and several structurally unrelated antioxidants inhibit atherosclerosis in animals. An emerging consensus also underscores the importance in vascular disease of oxidative events in addition to LDL oxidation. These include the production of reactive oxygen and nitrogen species by vascular cells, as well as oxidative modifications contributing to important clinical manifestations of coronary artery disease such as endothelial dysfunction and plaque disruption. Despite these abundant data however, fundamental problems remain with implicating oxidative modification as a (requisite) pathophysiologically important cause for atherosclerosis. These include the poor performance of antioxidant strategies in limiting either atherosclerosis or cardiovascular events from atherosclerosis, and observations in animals that suggest dissociation between atherosclerosis and lipoprotein oxidation. Indeed, it remains to be established that oxidative events are a cause rather than an injurious response to atherogenesis. In this context, inflammation needs to be considered as a primary process of atherosclerosis, and oxidative stress as a secondary event. To address this issue, we have proposed an “oxidative response to inflammation” model as a means of reconciling the response-to-injury and oxidative modification hypotheses of atherosclerosis.

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Section: Ldl Oxidation Versus Atherosclerosissupporting

confidence: 74%

Role of Oxidative Modifications in Atherosclerosis

Stocker¹,

Keaney²

2004

Physiological Reviews

2,258

1,756

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“…In one report, bacterial binding to Sp␣, a macrophageexpressed soluble protein, was found to be markedly higher in the presence of Ca 2ϩ than in the presence of EDTA (18). Further, a study with thioglycollate-elicited macrophages from wild-type and SR-A knock-out mice indicated that SR-A mediates cell adhesion to human smooth muscle cell-deposited extracellular matrix and that this function is partially dependent on divalent cations (51). Curiously, sequence alignment indicates that the residues involved in ion binding in MARCO (Asp 447 /Asp 448 , Glu 511 ) are present in the SRCR domain of SR-A (Fig.…”

Section: Expression Plasmidmentioning

confidence: 99%

Crystal Structure of the Cysteine-rich Domain of Scavenger Receptor MARCO Reveals the Presence of a Basic and an Acidic Cluster That Both Contribute to Ligand Recognition

Ojala

Pikkarainen

Tuuttila

et al. 2007

Journal of Biological Chemistry

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MARCO is a trimeric class A scavenger receptor of macrophages and dendritic cells that recognizes polyanionic particles and pathogens. The distal, scavenger receptor cysteine-rich (SRCR) domain of the extracellular part of this receptor has been implicated in ligand binding. To provide a structural basis for understanding the ligand-binding mechanisms of MARCO, we have determined the crystal structure of the mouse MARCO SRCR domain. The recombinant SRCR domain purified as monomeric and dimeric forms, and their structures were determined at 1.78 and 1.77 Å resolution, respectively. The monomer has a compact globular fold with a twisted five-stranded antiparallel ␤-sheet and a long loop covering a single ␣-helix, whereas the dimer is formed via ␤-strand swapping of two monomers, thus containing a large eight-stranded ␤-sheet. Calculation of the surface electrostatic potential revealed that the ␤-sheet region with several arginines forms a basic cluster. Unexpectedly, an acidic cluster was found in the long loop region. In the monomer, the acidic cluster is involved in metal ion binding. Studies with cells expressing various SRCR domain mutants showed that all of the arginines of the basic cluster are involved in ligand binding, suggesting a cooperative binding mechanism. Ligand binding is also dependent on the acidic cluster and Ca 2؉ ions whose depletion appears to affect ligand binding at least by modulating the electrostatic potential or relative domain orientation. We propose that the SRCR domain dimerization can contribute to the recognition of large ligands by providing a means for the MARCO receptor oligomerization.MARCO belongs to a diverse group of scavenger receptors (SRs) 3 expressed by macrophages, dendritic cells, and certain endothelial cells (1). These germ line-encoded receptors, also known as pattern recognition receptors due to their ability to recognize conserved pathogen-associated molecular patterns, are considered as an important part of innate immunity, the evolutionarily conserved, first line host defense mechanism. In addition to pathogen-associated molecular patterns, a long list of SR ligands, often polyanionic in nature, includes pollution particles, polyribonucleotides, bacterial lipopolysaccharides, modified host molecules such as oxidized low density lipoprotein (LDL), and unmodified endogenous proteins (1, 2). The SRs are classified into several subgroups, of which class A SRs have primarily been associated with innate immunity. This class consists of five members: SR-A (SR-AI, -II, and -III/ SCARA1) (3, 4), MARCO (macrophage receptor with collagenous domain)/SCARA2 (5), CSR1 (cellular stress response 1) and CSR2/SCARA3 (6), SRCL (scavenger receptor with C-type lectin) I and II/SCARA4 (7, 8), and Tesr (testis-expressed scavenger receptor)/SCARA5 (class A scavenger receptor 5) (9, 10). All of these are trimeric type II membrane proteins with a similar predicted tertiary structure consisting of a short intracellular domain, a transmembrane domain, and a large extracellular domain with...

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“…SR recognize a diverse array of ligands that may be loosely grouped into two categories: polyanionic compounds (e.g., polyinosinic acid, fucoidan, lipotechoic acid) and modified proteins [e.g., acetylated low-density lipoprotein (AcLDL), maleylated albumin, glycated collagen] (26). Other naturally occurring ligands include polynucleotides and polysaccharides, gram-positive and gram-negative bacteria, and apoptotic cells (16,53,67). The versatile biological functions of SR include the clearance of pathological substances, host defense, cell adhesion, activation of intracellular signaling events, and cytokine production (21,26,50,51,57,65), although it is not yet clear how SR coordinate these immune and homeostatic functions.…”

mentioning

confidence: 99%

Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure

Beamer¹,

Holian²

2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Alveolar macrophages express the class A scavenger receptor (CD204) (Babaev VR, Gleaves LA, Carter KJ, Suzuki H, Kodama T, Fazio S, and Linton MF. Arterioscler Thromb Vasc Biol 20: 2593–2599, 2000); yet its role in vivo in lung defense against environmental particles has not been clearly defined. In the current study, CD204 null mice (129Sv background) were used to investigate the link between CD204 and downstream events of inflammation and fibrosis following silica exposure in vivo. CD204−/− macrophages were shown to recognize and uptake silica in vitro, although this response was attenuated compared with 129Sv wild-type mice. The production of tumor necrosis factor-α in lavage fluid was significantly enhanced in CD204 null mice compared with wild-type mice following silica exposure. Moreover, after exposure to environmental particles, CD204−/− macrophages exhibited improved cell viability in a dose-dependent manner compared with wild-type macrophages. Finally, histopathology from a murine model of chronic silicosis in 129Sv wild-type mice displayed typical focal lesions, interstitial thickening with increased connective tissue matrix, and cellular infiltrate into air space. In contrast, CD204−/− mice exhibited little to no deposition of collagen, yet they demonstrated enhanced accumulation of inflammatory cells largely composed of neutrophils. Our findings point to an important role of CD204 in mounting an efficient and appropriately regulated immune response against inhaled particles. Furthermore, these results indicate that the functions of CD204 are critical to the development of fibrosis and the resolution of inflammation.

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The Class A Scavenger Receptor Binds to Proteoglycans and Mediates Adhesion of Macrophages to the Extracellular Matrix

Cited by 90 publications

References 38 publications

Role of Oxidative Modifications in Atherosclerosis

Role of Oxidative Modifications in Atherosclerosis

Crystal Structure of the Cysteine-rich Domain of Scavenger Receptor MARCO Reveals the Presence of a Basic and an Acidic Cluster That Both Contribute to Ligand Recognition

Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure

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