Macrophage scavenger receptor MARCO: In vitro and in vivo regulation and involvement in the anti-bacterial host defense

Laan, Luc J. W. van der; Kangas, Maarit; Döpp, E. A.; Broug-Holub, Ellen; Elomaa, Outi; Tryggvason, Karl; Kraal, Georg

doi:10.1016/s0165-2478(97)00077-1

Cited by 85 publications

(92 citation statements)

References 15 publications

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“…For blocking MARCO receptor, the macrophages were preincubated with ED31 10 g/ml as described previously. 4 One hour after incubation with C. parvum, numbers of macrophages ingesting C. parvum were counted. In all three experiments, more than three animals were examined.…”

Section: Cell Culturementioning

confidence: 99%

“…11 These scavenger receptors are divided into three classes: A, B, and C. [1][2][3][4][5][6][7][8][9][10][11] MSR-A and MARCO receptors are included in class A. MSR-A are trimeric membrane glycoproteins consisting of six domains: a C-terminal domain, a collagen-like domain, an ␣-helical coiled coil domain, a spacer domain, a transmembrane domain, and a cytoplasmic domain. 1,2 Although the C-terminal domain is type-specific (ie, different for each type of receptor), the collagen-like domain is common to both receptor types and is important for binding to ligands.…”

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confidence: 99%

“…13 The MARCO receptor is similar in molecular structure to MSR-A but different in that it has a long collagenlike domain and an extremely short ␣-helical coiled coil domain. [3][4][5] CD36 and SR-BI are class B receptors. 6 -8 CD36 is an 88-kd glycoprotein expressed on monocyte/ macrophages, platelets, and endothelial cells; it serves as a receptor for both the adhesive glycoprotein thrombospondin and collagen.…”

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Role of Macrophage Scavenger Receptors in Hepatic Granuloma Formation in Mice

Hagiwara

Takeya

Suzuki³

et al. 1999

The American Journal of Pathology

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Role of Macrophage Scavenger Receptors in Hepatic Granuloma Formation in Mice

Hagiwara

Takeya

Suzuki³

et al. 1999

The American Journal of Pathology

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“…It is expressed at significant levels only in the marginal zone macrophages of the spleen, in macrophages of the medullary cord of lymph nodes, and in the peritoneal macrophages (2). 4 In bacterial infections MARCO expression is up-regulated in macrophages of most tissues (3)(4)(5)(6). Cells transfected with a plasmid encoding MARCO avidly bind both Gram-negative and -positive bacteria, but not yeast (2,3).…”

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A Phage Display Screen and Binding Studies with Acetylated Low Density Lipoprotein Provide Evidence for the Importance of the Scavenger Receptor Cysteine-rich (SRCR) Domain in the Ligand-binding Function of MARCO

Chen

Sankala

Ojala

et al. 2006

Journal of Biological Chemistry

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MARCO is a class A scavenger receptor capable of binding both Gram-negative and -positive bacteria. Using the surface plasmon resonance technique, we show here that a recombinant, soluble form of MARCO, sMARCO, binds the major Gram-negative and -positive bacterial surface components, lipopolysaccharide and lipoteichoic acid. Yet, the interaction of these two polyanions with sMARCO is of much lower affinity than that of polyinosinic acid, a polyanionic inhibitor of bacterial binding to MARCO. To further elucidate the ligand-binding functions of MARCO, we performed a phage display screen with sMARCO. The screening resulted in the enrichment of only a handful of phage clones. Contrary to expectations, no polyanionic peptides, but only those with a predominantly hydrophobic nature, were enriched. One peptide, VRWGSFAAWL, was displayed on two-thirds of the phages recovered after four rounds of screening. The VRWGSFAAWL phage-sMARCO interaction had significantly slower dissociation kinetics than that between sMARCO and lipopolysaccharide or lipoteichoic acid. Further work with this phage, and the second most enriched phage, displaying the peptide RLNWAWWLSY, demonstrated that both peptides bind to the SRCR domain of MARCO, and that they probably bind to the same site. Data base searches suggested that the VRWGSFAAWL peptide represents complement component C4, but we could not convincingly confirm this suggestion. A study with chimeric scavenger receptors indicated that even minor sequence changes in the MARCO scavenger receptor cysteine-rich (SRCR) domain can have profound effects on the binding of the prototypic scavenger receptor ligand, acetylated low density lipoprotein. As shown by differential binding of glutathione S-transferase-VR-WGSFAAWL, these differences were very likely due to conformational changes. These findings led to experiments that demonstrated a crucial role of the SRCR domain for acetylated low density lipoprotein binding in MARCO. Thus, our results strengthen the notion that the SRCR domain is the major ligand-binding domain in MARCO. Furthermore, they suggest that the domain may contain multiple ligand-binding sites.MARCO, a close relative of scavenger receptor A (see Ref. 1), is a trimeric type II transmembrane protein with an N-terminal intracellular domain, a transmembrane domain, and an extracellular portion composed of a short spacer domain, a long triple-helical collagenous domain, and a C-terminal scavenger receptor cysteine-rich (SRCR) 3 domain (2). MARCO has a very restricted expression pattern in adult mice living under pathogen-free conditions. It is expressed at significant levels only in the marginal zone macrophages of the spleen, in macrophages of the medullary cord of lymph nodes, and in the peritoneal macrophages (2). 4 In bacterial infections MARCO expression is up-regulated in macrophages of most tissues (3-6). Cells transfected with a plasmid encoding MARCO avidly bind both Gram-negative and -positive bacteria, but not yeast (2, 3). MARCO also has other than microbial ligand...

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“…The scavenger receptor family includes two members in the SR-A subclass which are expressed on lung macrophages and dendritic cells, MARCO (Macrophage receptor with collagenous structure), and SR-AI/II (1, 2, 4). MARCO, like SR-AI/II, binds acetylated LDL and bacteria but not yeast (5)(6)(7). MARCO and SR-AI/II expressed on alveolar macrophages function to promote uptake and clearance of inhaled particles and bacteria (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Scavenger Receptors and Resistance to Inhaled Allergens

Kobzik¹

2008

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE 01-02-20072. REPORT TYPE Annual DATES COVERED SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTESOriginal contains colored plates: ALL DTIC reproductions will be in black and white. ABSTRACTAfter OVA sensitization and aerosol challenge, SR-AI/II and MARCO-deficient mice exhibited greater eosinophilic airway inflammation and airway hyperresponsiveness compared to wild-type mice. A role for simple SRA-mediated antigen clearance ('scavenging') by lung macrophages was excluded by observation of comparable uptake of fluorescent OVA by wild-type and SRA-deficient lung MΦs and DCs. In contrast, airway instillation of fluorescent antigen revealed significantly higher traffic of labelled DCs to thoracic lymph nodes in SRA-deficient mice than in controls. The increased migration of SRA-deficient DCs was accompanied by enhanced proliferation in thoracic lymph nodes of adoptively transferred OVA-specific T cells after airway OVA challenge. The data identify a novel role for SRAs expressed on lung DCs in down-regulation of specific immune responses to aero-allergens by reduction of DC migration from the site of antigen uptake to the draining lymph nodes. References……………………………………………………………………………. 5 SUBJECT TERMSAppendices…………………………………………………………………………… 5 4 INTRODUCTION: Narrative that briefly (one paragraph) describes the subject, purpose and scope of the research.Our central hypothesis is that lung macrophage scavenger receptors normally function to bind and clear inhaled allergens and pathogens, thereby preventing allergic responses and infections. The purpose of the project is to determine whether 1) decreased levels of SRAs (mediated by environmental stresses) increase susceptibility to asthma or pneumonia; and 2) therapy to increase or maintain normal levels of scavenger receptors will increase resistance to asthma and pneumonia. The scope of the research includes studies using in vivo mouse models (Aim 1), studies of the specific role of alveolar macrophages (Aim 2) and dendritic cells (Aim 3) and studies of the effec...

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Macrophage scavenger receptor MARCO: In vitro and in vivo regulation and involvement in the anti-bacterial host defense

Cited by 85 publications

References 15 publications

Role of Macrophage Scavenger Receptors in Hepatic Granuloma Formation in Mice

Role of Macrophage Scavenger Receptors in Hepatic Granuloma Formation in Mice

A Phage Display Screen and Binding Studies with Acetylated Low Density Lipoprotein Provide Evidence for the Importance of the Scavenger Receptor Cysteine-rich (SRCR) Domain in the Ligand-binding Function of MARCO

Scavenger Receptors and Resistance to Inhaled Allergens

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