Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease

Kelley, Jim; Ozment, Tammy R.; Li, Chuanfu; Schweitzer, John B.; Williams, David L.

doi:10.1615/critrevimmunol.2014010267

Cited by 135 publications

(126 citation statements)

References 155 publications

(237 reference statements)

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“…The class A macrophage scavenger receptor (SR-A) is a prototypic member of the scavenger receptor (SR) family, a collection of membrane receptors [20]. In recent years, several studies have revealed that SR-A has an essential influence on inflammation, ERS and cell apoptosis [21, 22]. Hydrogen sulfide (H 2 S), synthesized in the metabolic pathway that regulates the tissue concentration of sulfur-containing amino acids, is an endogenous gaseous mediator that exerts effects in the central nervous system and the cardiovascular system [23].…”

Section: Introductionmentioning

confidence: 99%

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Ling¹,

Yu²,

Wang³

et al. 2017

Cell Physiol Biochem

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Objective: This study aims to explore the effects of the exogenous hydrogen sulfide (H₂S)-mediated scavenger receptor A (SR-A) signaling pathway on renal ischemia/reperfusion injury (IRI) by regulating endoplasmic reticulum (ER) stress-induced autophagy in rats. Methods: A total of 48 normal Sprague-Dawley (SD) rats and SR-A knockout rats were selected and divided into six groups (n = 8): wild-type (WT) + sham, WT + ischemia-reperfusion (I/R), WT + I/R + NaHS, SR-A^-/- + sham, SR-A^-/- + I/R and SR-A^-/- + I/R + NaHS. The concentrations of urinary protein, blood urea nitrogen (BUN), serum creatinine (SCR), malondialdehyde (MDA) and H₂S in renal tissue were detected. qRT-PCR and Western blotting were used to detect the mRNA and protein levels of IL-6, TGF-β, SR-A, LC3I, LC3II, P62, PERK, ATF6 and IRE1 pathway-related genes. A TUNEL assay was used to detect cell apoptosis. Electron microscopy was applied to observe the structure of renal autophagosomes. Results: Compared with the WT + sham group, in the rates of the WT + I/R group, the urine volume, urinary protein, BUN, SCR and MDA concentrations, the mRNA and protein expression of IL-6, TGF-β, LC3II/I, and ER stress pathway-related genes, the cell apoptosis index, and the number of autophagosomes were significantly increased 24 h after I/R, while P62 and SR-A protein expression and SOD and H₂S concentrations were significantly decreased (all P < 0.05). The levels of renal injury, autophagy and ER stress pathway-related genes were decreased in the WT + I/R + NaHS group but were increased in the SR-A^-/- + I/R group relative to the WT + I/R group. No significant differences were observed in the urine volume; the concentrations of urinary protein, BUN, SCR and MDA; the SOD activity; the mRNA and protein expression of IL-6, TGF-β, SR-A, GRP78, SR-A, GPR94, ATF4, IRE1, XBP1, ATF6, and eIF2α; the cell apoptosis index; or the number of autophagosomes in rats of the SR-A^-/- + I/R and SR-A^-/- + I/R + NaHS groups (all P > 0.05). Conclusion: These results demonstrate that the exogenous H₂S-mediated SR-A signaling pathway reduces renal IRI injury by up-regulating ER stress-induced autophagy in rats.

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Section: Introductionmentioning

confidence: 99%

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Ling¹,

Yu²,

Wang³

et al. 2017

Cell Physiol Biochem

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“…Previously identified ligands included modified LDL variants, glycated albumin, glycated collagens, and b-amyloid fibrils. 30 Such modified proteins are undesirable in the circulation, which may explain why they are efficiently eliminated from the circulation by SR-AI. For FX, a rather distinct mechanism appears to be involved.…”

Section: Discussionmentioning

confidence: 99%

Macrophage receptor SR-AI is crucial to maintain normal plasma levels of coagulation factor X

Muczynski

Bazaa

Loubière

et al. 2016

Blood

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Key Points• SR-AI is the major receptor of FX at the macrophage surface.• Macrophages use SR-AI to control FX circulatory levels.Beside its classical role in the coagulation cascade, coagulation factor X (FX) is involved in several major biological processes including inflammation and enhancement of virusinduced immune responses. We recently reported that the long circulatory half-life of FX is linked to its interaction with liver-resident macrophages. Importantly, we now observed that macrophages, but not undifferentiated monocytes, support this interaction. Using cell biology approaches with primary and THP1-derived macrophages as well as transfected cells, we further identified the scavenger receptor type A member I (SR-AI) to be a macrophage-specific receptor for FX. This result was confirmed using SR-AI-deficient mice, which exhibit reduced circulating levels of FX in vivo and loss of FX-macrophage interactions in vitro. Binding studies using purified proteins revealed that FX binds specifically (half-maximal binding, 3 mg/mL) to the extracellular domain of SR-AI. Altogether, we demonstrate that macrophages regulate FX plasma levels in an SR-AI-dependent manner. (Blood. 2016;127(6):778-786)

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“…Specifically, computer modeling has suggested that the collagenous domain is responsible for mediating the uptake of negatively charged NMs [26] . Interestingly, SR-A receptors function by interacting with other membrane bound signaling and transport proteins to induce intracellular signaling pathways [27] . Signaling through SR-A can result in either pro-survival or pro-death pathways.…”

Section: Scavenger Receptor Class Amentioning

confidence: 99%

“…SR-A type receptors are primarily expressed on innate immune cells such as macrophages and dendritic cells where they facilitate endocytosis of ligands and cellular adhesion. SR-A type receptors are also expressed on the surface of fibroblasts, microglia, astrocytes, and endothelial, and epithelial cells [27] . Involvement of SR-A has been evaluated in a variety of diseases including atherosclerosis, sepsis, and bacterial and viral infections [27] .…”

Section: Scavenger Receptor Class Amentioning

confidence: 99%

Implications of Scavenger Receptors in the Safe Development of Nanotherapeutics

Shannahan

Bai

Brown

2015

Receptor Clin Invest

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Nanomaterials (NMs) are being utilized in a variety of biomedical applications including drug delivery, diagnostics, and therapeutic targeting. These applications are made possible due to the unique physicochemical properties that are exhibited at the nanoscale. To ensure safe development of NMs for clinical use, it is necessary to understand their interactions with cells and specifically cell surface receptors, which will facilitate either their toxicity and/or clinical function. Recently our research and others have investigated the role of scavenger receptors in mediating NM-cell interactions and responses. Scavenger receptors are expressed by a variety of cell types that are first to encounter NMs during clinical use such as macrophages and endothelial cells. Scavenger receptors are recognized to facilitate uptake of a wide variety of ligands ranging from foreign substances to endogenous lipids/proteins. While interaction of NMs with scavenger receptors may allow therapeutic targeting in some instances, it also presents a challenge for the stealth delivery of NMs and avoidance of the scavenging capability of this class of receptors. Due to their role in facilitating immune responses, scavenger receptor-mediated inflammation is also of concern following NM delivery. The research highlighted in this brief review intends to summarize our current understanding regarding the consequences of NM-scavenger receptor interactions.

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Scavenger Receptor-A (CD204): A Two-Edged Sword in Health and Disease

Cited by 135 publications

References 155 publications

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Roles of the Exogenous H2S-Mediated SR-A Signaling Pathway in Renal Ischemia/ Reperfusion Injury in Regulating Endoplasmic Reticulum Stress-Induced Autophagy in a Rat Model

Macrophage receptor SR-AI is crucial to maintain normal plasma levels of coagulation factor X

Implications of Scavenger Receptors in the Safe Development of Nanotherapeutics

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