Inhibition of Antigen Trafficking through Scavenger Receptor A

Raycroft, Maurice T.; Harvey, Bohdan P.; Bruck, Matthew J.; Mamula, Mark J.

doi:10.1074/jbc.m111.316356

Cited by 22 publications

(19 citation statements)

References 28 publications

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“…Inhibiting SR-A leads to reduced interaction between macrophages and other immune cells including B cells and T cells suggesting that a scavenger receptor deficiency in macrophages may influence their local immune environment. 27 Macrophages and neutrophils collaborate with each other in response to acute injury 28 ; for instance, neutrophils produce oxidized phospholipids and can assist with the recognition and recruitment of macrophages through scavenger receptors. 29 In atherosclerosis, recruited macrophages bearing scavenger receptors recognize and bind LDL from apoptotic cell populations including neutrophils, leading to the formation of foam cells.…”

Section: Discussionmentioning

confidence: 99%

The Role of Macrophage Class A Scavenger Receptors in a Laser-Induced Murine Choroidal Neovascularization Model

Jawad

Liu

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Laser-induced choroidal neovascularization (CNV) is a widely used model to mimic many features of CNV resulting from wet AMD. Macrophages have been implicated in the pathogenesis of AMD. Class A scavenger receptors, scavenger receptor-A (SR-A) and macrophage receptor with collagenous domain (MARCO), are expressed on macrophages and are associated with macrophage function. The goal of this study is to examine the role of macrophage scavenger receptors in immune cell recruitment and the formation of CNV. METHODS.Laser photocoagulation was performed in wild-type and knockout mice with deletion of SR-A (SR-A À/À ), MARCO (MARCO À/À ), or both SR-A and MARCO double knockout (DKO). Immune cell recruitment at different time points and CNV lesions at 14 days after laser treatment were evaluated through immunostaining and confocal microscopy. Microarray analysis was performed in eyes 1 day after laser injury. RESULTS.Wild-type eyes showed higher chemokine/receptor expression compared with knockout eyes after laser injury. Scavenger receptor deficiency markedly impaired the recruitment of neutrophils and macrophages to CNV lesions at 1-and 3-days post laser injury, respectively. Significantly reduced CNV volumes were found in the eyes from scavenger receptor knockout mice compared with wild-type mice.CONCLUSIONS. The deficiency of scavenger receptors impairs the formation of CNV and immune cell recruitment. Our findings suggest a potential role for scavenger receptors in contributing to CNV formation and inflammation in AMD.Keywords: AMD, CNV, macrophages, scavenger receptors A ge-related macular degeneration is the leading cause of irreversible central blindness in the elderly, worldwide. It is clinically characterized by degenerative changes in the macula, the region of the retina that permits fine central vision. One of the key pathologic features of AMD is the development of large drusen, extracellular deposits located in Bruch's membrane beneath the RPE. Their presence is a harbinger of further retinal change, the major risk factor for the development of advanced AMD, which can be classified into two subtypes: geographic atrophy (dry) and neovascular/exudative (wet). 1 In wet AMD, new vessels from the choroid breach Bruch's membrane and grow into the subretinal space and retina. This process is also called choroidal neovascularization (CNV). It represents only 10% of all cases of advanced AMD, but about 90% of AMD patients experience severe vision loss resulting from this subtype. Various animal models attempt to mimic the clinical manifestations of AMD. Among them, a laser-induced murine CNV model is widely used to mimic the wet form of AMD by compromising Bruch's membrane to induce CNV formation in the subretinal region. This model allows for visualization and evaluation of the morphologic changes of experimental CNV and has been a valuable tool to study the diverse components of complex CNV lesions. 2The exact mechanisms that cause AMD are not clear. Recent information suggests that immune mechanisms play...

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Section: Discussionmentioning

confidence: 99%

The Role of Macrophage Class A Scavenger Receptors in a Laser-Induced Murine Choroidal Neovascularization Model

Jawad

Liu

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…Longer duration of interactions between B cells and DC/MÈ can increase the accumulation of a particular Ag in the recipient DC/MÈ [129]. The amount of Ag accumulated could cross a threshold that directs recipient DC/MÈ activation or function.…”

Section: Epigenetic Defects Are Amplified In Antigen Presentationmentioning

confidence: 98%

Autoantigens: Novel forms and presentation to the immune system

et al. 2013

Self Cite

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It is clear that lupus autoimmunity is marked by a variety of abnormalities, including those found at a macroscopic scale, cells and tissues, as well as more microenvironmental influences, originating at the individual cell surface through to the nucleus. The convergence of genetic, epigenetic, and perhaps environmental influences all lead to the overt clinical expression of disease, reflected by the presences of autoantibodies and tissue pathology. This review will address several specific areas that fall among the non-genetic factors that contribute to lupus autoimmunity and related syndromes. In particular, we will discuss the importance of understanding various protein post-translational modifications (PTMs), mechanisms that mediate the ability of "modified self" to trigger autoimmunity, and how these PTMs influence lupus diagnosis. Finally, we will discuss altered pathways of autoantigen presentation that may contribute to the perpetuation of chronic autoimmune disease.

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“…Interestingly, a number of natural products have been reported as potential SRA inhibitors with varied biological activities. 16,17 Among them, sennoside B and tannic acid were able to reduce SRA mediated antigen transfer. 17 Particularly, sennoside B was shown to be able to reduce T cell proliferation both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

“…16,17 Among them, sennoside B and tannic acid were able to reduce SRA mediated antigen transfer. 17 Particularly, sennoside B was shown to be able to reduce T cell proliferation both in vitro and in vivo. However, the high molecular weight (>1,000) of most of these compounds makes them not suitable for further drug development.…”

Section: Introductionmentioning

confidence: 99%

Understanding molecular interactions between scavenger receptor A and its natural product inhibitors through molecular modeling studies

Pagare

Zaidi

Zhang

et al. 2017

Journal of Molecular Graphics and Modelling

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Scavenger receptor A (SRA), as an immune regulator, has been shown to play important roles in lipid metabolism, cardiovascular diseases, and pathogen recognition. Several natural product inhibitors of SRA have been studied for their potential application in modulating SRA functions. To understand the binding mode of these inhibitors on SRA, we conducted systematic molecular modeling studies in order to identify putative binding domain(s) that may be responsible for their recognition to the receptor as well as their inhibitory activity. Treatment of SRA with one of the natural product inhibitors, rhein, led to significant dissociation of SRA oligomers to its trimer and dimer forms, which further supported our hypothesis on their putative mechanism of action. Such information is believed to shed light on design of more potent inhibitors for the receptor in order to develop potential therapeutics through immune system modulation.

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Inhibition of Antigen Trafficking through Scavenger Receptor A

Cited by 22 publications

References 28 publications

The Role of Macrophage Class A Scavenger Receptors in a Laser-Induced Murine Choroidal Neovascularization Model

The Role of Macrophage Class A Scavenger Receptors in a Laser-Induced Murine Choroidal Neovascularization Model

Autoantigens: Novel forms and presentation to the immune system

Understanding molecular interactions between scavenger receptor A and its natural product inhibitors through molecular modeling studies

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