STRUCTURES AND FUNCTIONS OF MULTILIGAND LIPOPROTEIN RECEPTORS: Macrophage Scavenger Receptors and LDL Receptor-Related Protein (LRP)

Krieger, Monty; Herz, Joachim

doi:10.1146/annurev.bi.63.070194.003125

Cited by 1,102 publications

(854 citation statements)

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“…Due to differential accessibility of lysines on the BSA molecule and the increased blocking of free amines by maleyl groups, fluorescent labeling required increasing stoichiometric ratios of FITC to mal-BSA with higher degree of maleylation. Therefore FITC:protein ratios of 2:1, 5:1, 10:1, 20:1 and 30:1 were employed for BSA maleylated at 0%, [8][9][10][11][12][13][14][15][16][17][18][19][20].5%, 29-69%, 82%, and 89%, respectively. Briefly, FITC (10mg/ml in DMSO) was added to mal-BSA in small aliquots over the course of 1 hour at room temperature while stirred.…”

Section: Synthesis Of Fitc-mal-bsamentioning

confidence: 99%

“…(7,(16)(17)(18)(19)(20) Recognition is not dependent upon specific amino acid sequence or carbohydrate structures. Because of their role in inflammation, SR-A receptors are not down regulated with ligand concentration, mediate very efficient and rapid internalization of bound ligand, and repeatedly recycle through the endosomal compartment (21,22)-illustrating desirable traits as targets for labeling.…”

Section: Introductionmentioning

confidence: 99%

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Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

2006

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Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the subclinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI.

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Section: Synthesis Of Fitc-mal-bsamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

2006

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“…A number of investigations have suggested that macrophage scavenger receptors in mammals are involved in the recognition of apoptotic or senescent cells produced during development or in aging, as well as in the recognition of non-self' substances and atherogenic lipoproteins [23±25]. Scavenger receptors are defined as receptors for chemically modified low-density lipoprotein such as acetylated low-density lipoprotein (AcLDL), and are characterized by high-affinity and broad polyanionic ligand-specificity [23]. Because insect granulocytes are phagocytic cells like mammalian macrophages [26], these characteristics of scavenger receptors prompted us to examine whether the 120-kDa protein exhibits scavenger-receptor activity, since a possible function of the 120-kDa protein is assumed to be recognition and phagocytosis of apoptotic larval cells during metamorphosis.…”

Section: Possible Role Of the 120-kda Protein In Metamorphosismentioning

confidence: 99%

A novel hemocyte‐specific membrane protein of Sarcophaga (flesh fly)

Hori

Kobayashi

Natori

2000

European Journal of Biochemistry

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Extensive tissue remodeling takes place during metamorphosis of holometabolous insects. It has been shown that hemocytes play crucial roles in the recognition and elimination of apoptotic cells and larval tissue fragments produced during metamorphosis. We report the immunoaffinity purification, cDNA cloning, and characterization of a prepupal hemocyte membrane protein of Sarcophaga (flesh fly) with a molecular mass of 120 kDa. This protein is a novel type I transmembrane protein with 18 repeats of an epidermal growth factor-like domain in the predicted extracellular region. Expression of the protein was restricted exclusively to prepupal hemocytes. This protein is suggested to be a scavenger receptor for tissue remodeling.

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“…Class A macrophage scavenger receptor (SR-A) is a macrophage (M )-restricted multifunctional molecule (9). It can bind an unusually broad range of ligands, a property that underlies its many activities (9,10).…”

mentioning

confidence: 99%

“…It can bind an unusually broad range of ligands, a property that underlies its many activities (9,10). These ligands include modified lipoproteins, LPS of Gram-negative bacteria, and lipotechoic acid of Gram-positive species, ␤-amyloid, and advanced glycation end product (AGE).…”

mentioning

confidence: 99%

The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

Cotena

Gordon

Platt

2004

The Journal of Immunology

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The macrophage scavenger receptor (SR-A) is a multifunctional receptor that is associated with several important pathological conditions, including atherosclerosis. In this study, we show, using a sterile peritonitis model, that it can regulate the inflammatory response. SR-A null mice display an increased initial granulocytic infiltration because of overproduction of the CXC chemokines, MIP-2 and keratinocyte-derived cytokine. This differential response is dependent upon particle internalization and can be mimicked by advanced glycation end product-BSA-conjugated latex beads. Thus SR-A is a nonactivating receptor, which is the first example of a pattern recognition receptor that serves to counter the activities of proinflammatory receptors and attenuates the production of specific chemokines to ensure an inflammatory response of the appropriate magnitude.

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STRUCTURES AND FUNCTIONS OF MULTILIGAND LIPOPROTEIN RECEPTORS: Macrophage Scavenger Receptors and LDL Receptor-Related Protein (LRP)

Cited by 1,102 publications

References 0 publications

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

A novel hemocyte‐specific membrane protein of Sarcophaga (flesh fly)

The Class A Macrophage Scavenger Receptor Attenuates CXC Chemokine Production and the Early Infiltration of Neutrophils in Sterile Peritonitis

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