Affinage

MSR1

Macrophage scavenger receptor types I and II · UniProt P21757

Length
451 aa
Mass
49.8 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MSR1 (SR-A/CD204) is a class A scavenger receptor expressed on macrophages, dendritic cells, and neutrophils that mediates the recognition, binding, and endocytosis of a remarkably diverse array of ligands — including modified lipoproteins, amyloid-β, DAMPs (HMGB1, peroxiredoxins), dsRNA, von Willebrand factor, ferritin, complement iC3b, oxidized lipids, collagen monomers, and spectrin on dead cells — using its collagen-like domain for polyanionic ligands and its SRCR domain for Ca²⁺-dependent dead-cell recognition (PMID:23717201, PMID:31653705, PMID:29326120, PMID:28394332). Beyond endocytic clearance, MSR1 transduces intracellular signals: it recruits the TAK1/MKK7/JNK complex via K63-polyubiquitylation to switch M2 macrophages toward a pro-inflammatory state, directly binds TRAF6 to inhibit TLR4-NF-κB signaling independently of its ligand-binding domain, cooperates with Mertk to phosphorylate PLCγ2 during apoptotic cell ingestion, and activates PI3K/AKT/GSK3β/β-catenin and AMPK/mTOR pathways to regulate macrophage polarization, osteogenesis, and leukemia stem cell proliferation (PMID:31028084, PMID:21460221, PMID:18511575, PMID:31903103, PMID:21596859). On dendritic cells, MSR1 suppresses TLR-augmented CD4⁺ and CD8⁺ T cell priming by inhibiting STAT1, p38, and NF-κB, functioning as a negative regulator of adaptive immunity (PMID:19349620, PMID:22083206). MSR1 expression is transcriptionally controlled by MAFB downstream of retinoic acid receptor signaling, negatively regulated by PPARγ, and induced by LPS through the MAPK/ERK pathway (PMID:28394332, PMID:23333385, PMID:29032172).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 Medium

    The question of whether class A scavenger receptors differentially regulate cytokine output was addressed: SR-AI/II ligation suppresses IL-12 production in macrophages (opposite to MARCO), establishing MSR1 as an anti-inflammatory signal modulator rather than simply an endocytic receptor.

    Evidence MARCO-KO and SR-AI/II-KO peritoneal macrophages stimulated with LPS ± IFN-γ, IL-12 ELISA

    PMID:16339540

    Open questions at the time
    • Downstream signaling pathway from SR-AI ligation to IL-12 suppression not mapped
    • Single lab finding
  2. 2007 Medium

    MSR1's role in innate antimicrobial defense and oxidized lipid scavenging in the lung was established: SR-AI/II deficiency impaired bacterial phagocytosis and clearance of oxidized lipids in vivo, leading to enhanced inflammation and mortality.

    Evidence SR-AI/II-KO mice challenged intratracheally with pneumococci or oxidized lipids; in vivo phagocytosis, survival, and neutrophil influx quantified

    PMID:16675784 PMID:17332894

    Open questions at the time
    • Relative contribution of SR-AI vs. SR-AII isoforms not distinguished
    • Cooperation with MARCO not fully delineated
  3. 2008 Medium

    How MSR1 transduces signals during efferocytosis was unknown; co-immunoprecipitation revealed that SR-A associates with the receptor tyrosine kinase Mertk, and SR-A engagement by apoptotic cells triggers Mertk phosphorylation and downstream PLCγ2 activation required for ingestion.

    Evidence Co-IP in peritoneal macrophages, SR-A-KO macrophages showing reduced Mertk phosphorylation, apoptotic thymocyte uptake assay

    PMID:18511575

    Open questions at the time
    • Whether SR-A–Mertk interaction is direct or bridged by a co-receptor not resolved
    • Single lab
  4. 2009 High

    MSR1's immunosuppressive function on dendritic cells was demonstrated: SR-A/CD204-deficient DCs showed enhanced TLR4-augmented CD8⁺ T cell priming, establishing MSR1 as a negative regulator of adaptive immunity beyond its macrophage roles.

    Evidence SR-A-KO mice and siRNA-silenced DCs, antigen-specific T cell activation assays, tumor challenge models

    PMID:19349620

    Open questions at the time
    • Precise signaling pathway in DCs linking SR-A to T cell suppression not fully mapped
  5. 2011 High

    The mechanism of MSR1-mediated NF-κB suppression was resolved: MSR1 directly binds the TRAF-C domain of TRAF6, inhibiting TRAF6 dimerization and ubiquitination, thereby attenuating TLR4 signaling independently of MSR1's ligand-binding and endocytic functions.

    Evidence Co-IP with domain mutagenesis, NF-κB reporter assays, SR-A-KO macrophages and DCs, in vivo LPS endotoxic shock model

    PMID:21460221

    Open questions at the time
    • Structural basis of the MSR1–TRAF6 interaction not determined
    • Whether this mechanism operates in all MSR1-expressing cell types is untested
  6. 2011 Medium

    MSR1 was shown to function as a tumor suppressor in leukemia stem cells: BCR-ABL downregulates Msr1, and Msr1 deletion accelerates CML by enhancing LSC self-renewal through the PI3K-AKT/β-catenin pathway, revealing a non-immune role for MSR1.

    Evidence BCR-ABL-induced CML mouse model crossed with Msr1-KO, microarray, cell cycle and apoptosis assays

    PMID:21596859

    Open questions at the time
    • How BCR-ABL transcriptionally silences Msr1 not defined
    • Relevance to human CML not validated
    • Single lab
  7. 2013 High

    MSR1's ligand repertoire was expanded to include dsRNA and soluble amyloid-β with defined domain requirements: basic residues in the collagen-like domain mediate dsRNA binding and transport to TLR3-containing endosomes, while Scara1 deficiency accelerates Aβ accumulation in Alzheimer's models.

    Evidence RNAi knockdown/exogenous rescue in hepatocytes for dsRNA/TLR3; Scara1-null × PS1-APP mouse cross for Aβ clearance

    PMID:23717201 PMID:23799536

    Open questions at the time
    • Whether dsRNA transport and Aβ clearance use overlapping or distinct endosomal pathways unknown
  8. 2013 Medium

    Transcriptional regulation of MSR1 was clarified: PPARγ negatively regulates MSR1 expression, as demonstrated by LOX-1 abrogation-induced MSR1 upregulation reversed by PPARγ agonist.

    Evidence LOX-1-KO macrophages, troglitazone (PPARγ agonist) rescue, mRNA/protein quantification

    PMID:23333385

    Open questions at the time
    • Whether PPARγ directly binds the MSR1 promoter not tested
    • Single lab
  9. 2016 Medium

    Post-translational regulation of MSR1 function was defined: dual N-glycosylation sites are critical for oligomeric Aβ internalization, even when surface targeting is preserved, establishing glycosylation as a determinant of ligand-specific receptor function.

    Evidence N-glycosylation site mutagenesis, surface targeting vs. oAβ internalization assays in transfected cells

    PMID:26892079

    Open questions at the time
    • In vivo relevance of glycosylation-dependent Aβ uptake not demonstrated
    • Single lab
  10. 2017 High

    MSR1 was established as a central DAMP clearance receptor in ischemic brain, with its transcription controlled by MAFB: combined Msr1/Marco deficiency in myeloid cells impaired DAMP clearance, worsened neuroinflammation, and exacerbated neuronal injury in stroke.

    Evidence Msr1/Marco-KO mice in ischemic stroke model, MAFB-deficient mice, in vitro DAMP internalization assays, Am80 pharmacological rescue

    PMID:28394332

    Open questions at the time
    • Individual contribution of Msr1 vs. Marco to each DAMP class in vivo not fully separated
  11. 2017 Medium

    LPS-induced MSR1 upregulation was mapped to the MAPK/ERK pathway: MEK inhibitors specifically blocked LPS-induced CD204 expression and acetylated-LDL uptake without affecting CD36, separating the transcriptional control of these two scavenger receptors.

    Evidence Mouse bone marrow macrophages treated with LPS ± MEK inhibitors (U0126, PD0325901), CD204/CD36 expression and Ac-LDL uptake

    PMID:29032172

    Open questions at the time
    • Transcription factor downstream of ERK that directly activates MSR1 promoter not identified
    • Single lab
  12. 2018 High

    MSR1 was identified as a clearance receptor for von Willebrand factor, binding VWF in a calcium-dependent manner via VWF A1/D4 domains; SR-AI deficiency reduced VWF clearance in vivo and VWF gain-of-clearance mutants showed enhanced SR-AI binding.

    Evidence Purified SR-AI binding assays, SR-AI-KO mice with hydrodynamic VWF gene transfer, VWF mutant binding studies

    PMID:29326120

    Open questions at the time
    • Relative contribution of MSR1 vs. other VWF clearance receptors (LRP1, ASGPR) not quantified
  13. 2019 High

    The intracellular signaling mechanism of MSR1 on phagosomes was elucidated: K63-polyubiquitylation of MSR1 recruits the TAK1/MKK7/JNK complex, driving pro-inflammatory reprogramming of M2 macrophages, revealing how MSR1 converts from scavenger to signal transducer.

    Evidence Phagosomal proteomics, K63-ubiquitylation assays, MSR1-KO macrophages, JNK inhibition, human ovarian cancer tissue validation

    PMID:31028084

    Open questions at the time
    • E3 ligase responsible for K63-ubiquitylation of MSR1 not identified
    • Whether this phagosomal signaling occurs with all MSR1 ligands unknown
  14. 2019 High

    The structural basis of MSR1-mediated dead cell recognition was solved: crystal structure of the SRCR domain at 1.8 Å revealed a Ca²⁺-binding site, and mass spectrometry identified spectrin as the specific dead-cell ligand recognized by the SRCR domain.

    Evidence X-ray crystallography, mass spectrometry, SRCR domain mutagenesis, cell-based internalization assays

    PMID:31653705

    Open questions at the time
    • How SRCR-mediated and collagen-domain-mediated ligand recognition are coordinated in the native trimer unknown
  15. 2020 Medium

    MSR1-mediated PI3K/AKT/GSK3β/β-catenin signaling in macrophages was linked to M2 polarization and osteogenic differentiation: MSR1 activates this pathway targeting PGC1α to enhance mitochondrial oxidative phosphorylation and promote bone formation in vivo.

    Evidence MSR1-KO mice in tibial defect model, BMDM/BMSC co-culture, RNA-seq, Western blotting

    PMID:31903103

    Open questions at the time
    • How MSR1 activates PI3K — direct interaction vs. co-receptor involvement — not resolved
    • Single lab
  16. 2022 High

    MSR1 was identified as a ferritin receptor on neutrophils that triggers NETosis (via PAD4, NE, ROS), establishing a new cell-type-specific function; Msr1 ablation protected mice from ferritin-induced hyperinflammation, relevant to adult-onset Still's disease.

    Evidence Msr1-KO mice with ferritin administration, neutrophil depletion, NET formation assays, AOSD patient validation

    PMID:36357401

    Open questions at the time
    • Downstream signaling events between MSR1 engagement and PAD4/ROS activation on neutrophils not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the E3 ubiquitin ligase responsible for K63-polyubiquitylation of MSR1, the structural basis of the MSR1–TRAF6 interaction, how the collagen-like domain and SRCR domain coordinate ligand discrimination in the native trimer, and whether MSR1's diverse signaling outputs (JNK, NF-κB suppression, PI3K/AKT, AMPK/mTOR) are selected by specific ligands or by cell-type context.
  • No E3 ligase identified for MSR1 K63-ubiquitylation
  • No full-length MSR1 trimer structure available
  • Ligand-specific vs. cell-type-specific signaling determinants unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0038024 cargo receptor activity 6 GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 6 GO:0005768 endosome 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 6 R-HSA-5357801 Programmed Cell Death 2 R-HSA-109582 Hemostasis 1
Partners
MAFBMERTKMKK7SPTBN1TAK1TRAF6

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2017 MSR1 (SR-A/CD204) internalizes DAMPs including HMGB1, peroxiredoxins, and S100A8/S100A9 in vitro; in ischemic brain, DAMP internalization is largely mediated by MSR1, and its expression is controlled by the transcription factor MAFB. Combined deficiency of Msr1 and Marco in infiltrating myeloid cells caused impaired DAMP clearance, more severe inflammation, and exacerbated neuronal injury in murine ischemic stroke. In vitro internalization assays, murine ischemic stroke model (Msr1/Marco knockout), MAFB-deficient mice, transcription factor analysis Nature medicine High 28394332
2013 Scara1 (MSR1/CD204) acts as a receptor for soluble amyloid-β on myeloid cells; Scara1 deficiency accelerates Aβ accumulation and increases mortality in a PS1-APP Alzheimer's mouse model, while pharmacological upregulation of Scara1 on mononuclear phagocytes increases Aβ clearance. shRNA screening, Scara1 null × PS1-APP mouse cross, in vivo Aβ clearance assay, pharmacological upregulation Nature communications High 23799536
2019 Triggering of MSR1 in IL-4-activated (M2) macrophages recruits the TAK1/MKK7/JNK signalling complex to phagosomes via K63 polyubiquitylation of MSR1, leading to enhanced JNK activation and a phenotypic switch from anti-inflammatory to pro-inflammatory state; this effect is abolished upon MSR1 deletion or JNK inhibition. Proteomics of phagosomal fractions, MSR1 knockout macrophages, K63-ubiquitylation assays, JNK inhibition, IL-4 stimulation, human ovarian cancer tissue validation The EMBO journal High 31028084
2011 SRA/CD204 (MSR1) directly interacts with the TRAF-C domain of TRAF6, inhibiting TRAF6 dimerization and ubiquitination, thereby suppressing TLR4-induced NF-κB activation. This regulatory function is independent of MSR1's ligand-binding domain, uncoupling its signaling-regulatory role from its endocytic function. Co-immunoprecipitation, domain mutagenesis, NF-κB reporter assays, SR-A/CD204 knockout macrophages and dendritic cells, LPS endotoxic shock model The Journal of biological chemistry High 21460221
2013 MSR1 (class A scavenger receptor type 1) binds extracellular dsRNA, mediates its endocytosis and transport to the endosome where TLR3 is engaged, triggering IFN responses in hepatocytes. A series of conserved basic residues in the carboxy-terminus of the collagen superfamily domain are required for dsRNA binding and transport. RNAi-mediated MSR1 knockdown blocks TLR3 sensing of HCV; exogenous MSR1 expression restores TLR3 signaling. RNAi knockdown, exogenous MSR1 overexpression, domain mutagenesis (collagen superfamily domain basic residues), HCV infection assay in hepatocyte cultures, IFN response measurement PLoS pathogens High 23717201
2008 SR-AI (MSR1) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake. SR-A associates with Mertk (directly or indirectly), and apoptotic cell exposure induces SR-A–dependent phosphorylation of Mertk and downstream phospholipase Cγ2, which are required for apoptotic cell ingestion. SR-A−/− macrophages show reduced and delayed Mertk phosphorylation and impaired apoptotic cell ingestion. Western blotting, co-immunoprecipitation, anti-SR-A blocking antibodies, SR-A−/− peritoneal macrophages, dexamethasone-induced apoptotic thymocytes Journal of leukocyte biology Medium 18511575
2009 SRA/CD204 (MSR1) expressed on dendritic cells negatively regulates TLR4 agonist-augmented CD8+ T cell activation; SRA/CD204-deficient DCs display enhanced immunostimulatory activity upon TLR4 engagement, and siRNA silencing of SRA/CD204 in DCs improves antigen-specific CD8+ T cell priming. SRA/CD204-deficient mice, siRNA-mediated knockdown in DCs, TLR4 agonist stimulation, antigen-specific T cell priming assays, tumor challenge models Blood High 19349620
2011 SRA/CD204 (MSR1) on dendritic cells suppresses CD4+ T cell activation by inhibiting STAT1, p38 MAPK, and NF-κB signaling in DCs; this suppressive activity is independent of classical endocytic function of SR-A/CD204, and absence of SR-A leads to elevated IL-12p35 expression upon CD40 ligation plus IFN-γ stimulation. SRA−/− mice, OT-II adoptive transfer, in vitro DC stimulation, STAT1/p38/NF-κB pathway analysis, anti-CD40 + IFN-γ treatment Journal of molecular medicine Medium 22083206
2011 SRA/CD204 (MSR1) directly interacts with exogenous hsp110; lack of SRA/CD204 reduces hsp110 binding and internalization by DCs but paradoxically enhances T cell stimulation via increased NF-κB activation, demonstrating an immunosuppressive signaling role for SRA/CD204 independent of antigen internalization. Direct binding assay (hsp110 to DCs ± SRA/CD204), SRA−/− DCs, NF-κB activation assays, antigen-specific T cell stimulation, shRNA lentiviral silencing, in vivo melanoma vaccine model Journal of immunology Medium 21832164
2019 SCARA1 (MSR1/CD204) recognizes dead cells specifically through its SRCR domain in a Ca2+-dependent manner, and cellular spectrin (via SPEC repeats) is the binding target of SCARA1 on dead cells. Crystal structure of the SRCR domain (1.8 Å) reveals its Ca2+-binding site. Macrophages internalize dead cells/debris via the SCARA1–spectrin interaction. Crystal structure determination (1.8 Å), mass spectrometry identification of binding partners, biochemical binding assays, cell-based internalization assays, SRCR domain mutagenesis, Ca2+-dependence assays The Journal of biological chemistry High 31653705
2018 SR-AI (MSR1) on macrophages functions as a clearance receptor for von Willebrand factor (VWF); VWF binding is calcium-dependent and involves the A1 and D4 domains of VWF. SR-AI deficiency in mice reduces VWF clearance. VWF mutants with increased clearance (p.R1205H, p.S2179F) show enhanced binding to SR-AI. Purified SR-AI binding assay (half-maximum binding measured), SR-AI−/− macrophage binding experiments, hydrodynamic gene transfer in SR-AI−/− mice, antibody inhibition, VWF propeptide/antigen ratio as clearance marker Haematologica High 29326120
2013 SR-AI (MSR1) mediates opsonin-independent uptake of dextran-coated superparamagnetic iron oxide (SPIO) nanoparticles via its positively charged collagen-like domain; recognition of the iron oxide crystalline surface is sterically hindered by larger polymer coatings, and computer modeling reveals complementarity between Fe-OH groups on magnetite and charged lysines in the collagen-like domain. SR-AI transfected cells, J774 macrophages, nanoparticles with varied surface coatings, blocking antibodies, computer molecular modeling ACS nano Medium 23614696
2011 MSR1 has a tumor suppressor function in leukemia stem cells (LSCs) of CML: BCR-ABL downregulates Msr1, Msr1 deletion accelerates CML development and markedly increases LSC function by affecting cell cycle progression and apoptosis, and Msr1 exerts its effects through the PI3K-AKT pathway and β-Catenin. BCR-ABL–induced CML mouse model, Msr1 knockout mice, DNA microarray, gene expression analysis, cell cycle and apoptosis assays, PI3K-AKT and β-catenin pathway analysis Blood Medium 21596859
2020 Macrophage MSR1 promotes osteogenic differentiation of BMSCs via PI3K/AKT/GSK3β/β-catenin signaling in a co-culture system, and MSR1-activated PI3K/AKT/GSK3β/β-catenin pathway targets PGC1α to facilitate M2-like macrophage polarization by enhancing mitochondrial oxidative phosphorylation. MSR1 knockout mice show delayed intramembranous ossification. MSR1 KO mice (tibial monocortical defect model), BMDM/RAW264.7/BMSC co-culture system, qPCR, Western blotting, immunofluorescence, RNA sequencing Theranostics Medium 31903103
2020 MSR1 promotes phagocytosis of myelin debris and foamy macrophage formation after spinal cord injury; in the presence of myelin debris, MSR1-mediated NF-κB signaling drives release of inflammatory mediators and subsequent neuronal apoptosis. MSR1 KO mice show improved recovery from SCI. MSR1 KO mice (SCI model), in vitro macrophage/RAW264.7 treatment with myelin debris, qPCR, Western blotting, immunofluorescence, NF-κB pathway analysis Journal of neuroinflammation Medium 32066456
2022 Ferritin acts as a ligand for Msr1 on neutrophils, triggering NET formation through Msr1; ferritin exposure increases Msr1 surface expression on neutrophils and activates NET formation dependent on peptidylarginine deiminase 4, neutrophil elastase, and ROS production. Msr1 ablation protects mice from ferritin-induced tissue damage and hyperinflammatory response. Ferritin administration mouse model, Msr1 knockout mice, neutrophil depletion, surface receptor expression assays, NET formation assays (PAD4, NE, ROS), AOSD patient samples Nature communications High 36357401
2013 Monomeric collagen type I via CD204 (MSR1) induces phospho-Akt expression in alveolar macrophages, shifting them to the profibrotic M2 type and driving CCL18, IL-1ra, and CCL2 production; these effects are abrogated by neutralizing anti-CD204 antibody and PI3K inhibitor LY294002. Alveolar macrophage culture with collagen monomers, neutralizing anti-CD204 antibody, PI3K inhibitor (LY294002), ELISA, phospho-Akt ELISA, RT-PCR, flow cytometry PloS one Medium 24278429
2007 SR-AI/II (MSR1) contributes to innate lung defense against pneumococcal bacteria: SR-AI/II deficiency causes impaired phagocytosis of bacteria in vivo, diminished bacterial clearance from the lungs, increased pneumonic inflammation, and increased mortality in pneumococcal lung infection. SR-AI/II-deficient mice, intratracheal pneumococcal challenge, in vivo phagocytosis assay with fluorescent bacteria, survival studies, inflammatory cytokine measurement American journal of respiratory cell and molecular biology Medium 16675784
2007 MARCO and SR-AI/II (MSR1) on alveolar macrophages scavenge oxidized lipids (β-epoxide and PON-GPC) from lung lining fluid; SR-AI/II−/− mice show enhanced acute lung inflammation after intratracheal instillation of oxidized lipids, and normal AMs show greater uptake of β-epoxide compared with MARCO−/− AMs, consistent with SRA function in binding oxidized lipids. SR-AI/II−/− and MARCO−/− mice, intratracheal lipid instillation, in vitro uptake assay, neutrophil influx quantification, ozone exposure model The Journal of clinical investigation Medium 17332894
2005 SR-AI/II (MSR1/CD204) ligation inhibits IL-12 production in macrophages (opposite to MARCO), and SR-AI/II−/− peritoneal macrophages produce significantly more IL-12 in response to LPS or LPS+IFN-γ. SR-A mediates opsonin-independent phagocytosis in IL-4-pretreated cells. SR-A and MARCO are regulated in opposite directions by Th1/Th2 factors. MARCO-deficient and SR-AI/II-deficient mice, peritoneal macrophage isolation, IL-12 ELISA, immobilized mAb ligation, cytokine stimulation, phagocytosis assays Journal of immunology Medium 16339540
2013 Macrophage scavenger receptor Msr1 (SR-A) regulates the concentration of soluble autoantigen glucose-6-phosphate isomerase; Msr1−/− macrophages are inefficient at taking up this autoantigen, leading to elevated serum concentrations. This prevents pathogenic autoantibody production and protects from arthritis in the K/BxN model. Bone marrow transplant experiments confirm the macrophage-intrinsic mechanism. Msr1−/− × K/BxN mice, bone marrow transplantation, autoantigen uptake assay, serum glucose-6-phosphate isomerase measurement, autoantibody production, T and B cell activation analysis Journal of immunology Medium 23794629
2010 SR-AI (MSR1) recognizes complement iC3b (but not C3 or C3b) and mediates NF-κB activation and IL-8 production in response to iC3b-opsonized bacteria. The SRCR domain of SR-AI is essential for binding to serum-sensitized bacteria, identifying SR-AI as a complement receptor. SR-AI expressed in HEK 293T cells, E. coli challenge with fresh vs. heat-inactivated serum, anti-C3 antibody inhibition, purified iC3b binding, SRCR domain mutagenesis, NF-κB and IL-8 assays Protein & cell Medium 21203986
2022 MSR1 mediates M2 macrophage polarization by regulating arginine and proline metabolism, activating the AMPK/mTOR pathway; MSR1 knockdown inhibits M2 polarization and the malignant behavior of gastric cancer cells induced by M2 macrophages. ATAC-seq, RNA-seq, scRNA-seq, MSR1 siRNA knockdown, AMPK/mTOR pathway analysis, co-culture of macrophages with gastric cancer cells, CIBERSORTx algorithm International immunopharmacology Medium 36095948
2016 N-glycosylation of SR-AI (MSR1) at dual N-glycosylation sites (N120Q-N143Q and N143Q-N184Q) is critical for oligomeric amyloid-β internalization; mutations at these sites diminish oAβ internalization even when receptors are normally surface-targeted. SRCR domain mutations affecting β-sheet/α-helix structure obstruct N-glycosylation and surface targeting. SR-AI mutagenesis (N-glycosylation sites and SRCR domain), transfection and surface targeting assay, oAβ internalization assay, MARCO-SRCR mutant analysis Journal of biomedical science Medium 26892079
2022 MSR1 is a required component of the Mafb/Msr1/PI3K-Akt/NF-κB pathway downstream of RARα activation; Msr1 siRNA blocks RARα agonist (Am80)-induced Akt phosphorylation and anti-inflammatory effects after subarachnoid hemorrhage, and MSR1 promotes M1-to-M2 microglial polarization via this pathway. SAH rat model, RARα agonist (Am80), Msr1 siRNA, PI3K inhibitor (LY294002), Western blotting, immunofluorescence, BV2/SH-SY5Y co-culture in vitro SAH model Frontiers in immunology Medium 35237277
2022 MSR1 is identified as a receptor for ferritin on neutrophils (as well as macrophages), and mediates NET formation-dependent cytokine storm. Activation of MSR1 by ferritin triggers the NETosis pathway (PAD4, NE, ROS). This is relevant to adult-onset Still's disease where enhanced MSR1 signaling on neutrophils is observed. Msr1 KO mouse model, ferritin administration, neutrophil depletion, NET formation assays, MSR1 surface expression flow cytometry, AOSD patient validation Nature communications High 36357401
2022 Fatty acids derived from apoptotic chondrocytes are taken up by macrophages mainly through MSR1, subsequently activating PPARα to facilitate lipid droplet generation and fatty acid oxidation (FAO), which upregulates BMP7 via NAD+/SIRT1/EZH2 epigenetic axis to enhance osteoinductive function. MSR1 KO mice (endochondral ossification model), in vitro fatty acid uptake assay, PPARα activation, FAO measurement, BMP7 expression, NAD+/SIRT1/EZH2 pathway analysis Redox biology Medium 35525025
2013 LOX-1 abrogation induces MSR1 upregulation (nearly 100% increase at mRNA and protein levels) and CD36 downregulation in macrophages through decreased PPAR-γ expression; PPAR-γ agonist (troglitazone) treatment reverses MSR1 upregulation, identifying PPAR-γ as a negative regulator of MSR1 expression downstream of LOX-1. LOX-1 KO macrophages, ox-LDL stimulation, PPAR-γ agonist treatment, mRNA and protein quantification, Dil-ox-LDL uptake assay Biochemical and biophysical research communications Medium 23333385
2017 LPS enhances CD204 (MSR1) expression and acetylated-LDL uptake in bone marrow macrophages through the MAPK/ERK pathway; MEK inhibitors (U0126, PD0325901) block LPS-induced CD204 expression and Ac-LDL uptake but not CD36 expression, which is regulated through an ERK-independent pathway. Mouse bone marrow macrophages, LPS treatment, MEK inhibitors (U0126, PD0325901), Ac-LDL uptake assay, CD204/CD36 expression analysis Atherosclerosis Medium 29032172
2018 JNK1 (but not JNK2) mediates LPS-induced SR-AI (MSR1) and CD14 expression in macrophages, controlling LPS-induced oxLDL uptake and foam cell formation; JNK isoform-specific siRNA knockdown demonstrated the isoform specificity. JNK isoform-specific siRNA, pharmaceutical JNK inhibitor (SP600125), MEK inhibitor (U0126), p38 inhibitor (SB203580), LPS treatment, oxLDL uptake assay, SR-AI/CD14 expression analysis Frontiers in physiology Medium 29354064
2007 SR-AI (MSR1) is identified as a cellular receptor for Tamm-Horsfall protein with lower affinity than SREC-I (802 nM vs. 16.8 nM). Interaction is blocked by AcLDL, and SR-AI uptake of THP may play a role in local host defense. Retroviral expression cloning, affinity binding assays, blocking experiments with AcLDL and anti-receptor antibodies Journal of leukocyte biology Low 17928461

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Macrophage MSR1 promotes BMSC osteogenic differentiation and M2-like polarization by activating PI3K/AKT/GSK3β/β-catenin pathway. Theranostics 246 31903103
2017 MAFB prevents excess inflammation after ischemic stroke by accelerating clearance of damage signals through MSR1. Nature medicine 192 28394332
2013 Scara1 deficiency impairs clearance of soluble amyloid-β by mononuclear phagocytes and accelerates Alzheimer's-like disease progression. Nature communications 176 23799536
2013 Tumor associated macrophage expressing CD204 is associated with tumor aggressiveness of esophageal squamous cell carcinoma. Cancer science 160 23648122
2010 Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 150 20802348
2017 CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma. Scientific reports 135 28496107
2014 Scavenger receptor-A (CD204): a two-edged sword in health and disease. Critical reviews in immunology 122 24941076
2006 The macrophage scavenger receptor SR-AI/II and lung defense against pneumococci and particles. American journal of respiratory cell and molecular biology 120 16675784
2020 Metabolic characterisation of Magnetospirillum gryphiswaldense MSR-1 using LC-MS-based metabolite profiling. RSC advances 104 35516490
2007 Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II. The Journal of clinical investigation 102 17332894
2022 Activation of RARα Receptor Attenuates Neuroinflammation After SAH via Promoting M1-to-M2 Phenotypic Polarization of Microglia and Regulating Mafb/Msr1/PI3K-Akt/NF-κB Pathway. Frontiers in immunology 99 35237277
2022 The role of macrophage scavenger receptor 1 (MSR1) in inflammatory disorders and cancer. Frontiers in immunology 93 36325338
2011 Germline mutations in MSR1, ASCC1, and CTHRC1 in patients with Barrett esophagus and esophageal adenocarcinoma. JAMA 90 21791690
2013 Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation. PloS one 87 24278429
2005 Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO. Journal of immunology (Baltimore, Md. : 1950) 85 16339540
2019 Triggering MSR1 promotes JNK-mediated inflammation in IL-4-activated macrophages. The EMBO journal 82 31028084
2014 Coexpression of CD44-positive/CD133-positive cancer stem cells and CD204-positive tumor-associated macrophages is a predictor of survival in pancreatic ductal adenocarcinoma. Cancer 81 24839953
2011 Pattern recognition scavenger receptor CD204 attenuates Toll-like receptor 4-induced NF-kappaB activation by directly inhibiting ubiquitination of tumor necrosis factor (TNF) receptor-associated factor 6. The Journal of biological chemistry 78 21460221
2020 Macrophage MSR1 promotes the formation of foamy macrophage and neuronal apoptosis after spinal cord injury. Journal of neuroinflammation 76 32066456
2008 The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages. Journal of leukocyte biology 75 18511575
2005 Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure. American journal of physiology. Lung cellular and molecular physiology 75 15849212
2009 Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling-dependent CD8 T-cell activation. Blood 69 19349620
2007 Purified and sterilized magnetosomes from Magnetospirillum gryphiswaldense MSR-1 were not toxic to mouse fibroblasts in vitro. Letters in applied microbiology 69 17594464
2013 Class A scavenger receptor 1 (MSR1) restricts hepatitis C virus replication by mediating toll-like receptor 3 recognition of viral RNAs produced in neighboring cells. PLoS pathogens 66 23717201
2022 Ferritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still's disease pathogenesis. Nature communications 63 36357401
2008 Ferrous iron transport protein B gene (feoB1) plays an accessory role in magnetosome formation in Magnetospirillum gryphiswaldense strain MSR-1. Research in microbiology 63 18639631
2012 The class A macrophage scavenger receptor CD204 is a useful immunohistochemical marker of canine histiocytic sarcoma. Journal of comparative pathology 60 22901707
2015 Characterization of the plant growth promoting bacterium, Enterobacter cloacae MSR1, isolated from roots of non-nodulating Medicago sativa. Saudi journal of biological sciences 58 26858542
2011 Semicontinuous culture of Magnetospirillum gryphiswaldense MSR-1 cells in an autofermentor by nutrient-balanced and isosmotic feeding strategies. Applied and environmental microbiology 58 21724877
2008 High-yield growth and magnetosome formation by Magnetospirillum gryphiswaldense MSR-1 in an oxygen-controlled fermentor supplied solely with air. Applied microbiology and biotechnology 56 18425510
2007 Scavenger Receptors SR-AI/II and MARCO limit pulmonary dendritic cell migration and allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 55 17442975
2011 Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204). Biochemical and biophysical research communications 51 21756882
2013 Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI. ACS nano 49 23614696
2019 Elevation of pulmonary CD163+ and CD204+ macrophages is associated with the clinical course of idiopathic pulmonary fibrosis patients. Journal of thoracic disease 47 31656675
2014 Potential pathological roles for oxidized low-density lipoprotein and scavenger receptors SR-AI, CD36, and LOX-1 in aortic valve stenosis. Atherosclerosis 44 24929820
2011 Targeting the immunoregulator SRA/CD204 potentiates specific dendritic cell vaccine-induced T-cell response and antitumor immunity. Cancer research 43 21914786
2003 No association of germline alteration of MSR1 with prostate cancer risk. Nature genetics 42 12958598
2012 FeoB2 Functions in magnetosome formation and oxidative stress protection in Magnetospirillum gryphiswaldense strain MSR-1. Journal of bacteriology 40 22636767
2010 Single and multivariate associations of MSR1, ELAC2, and RNASEL with prostate cancer in an ethnic diverse cohort of men. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 40 20086112
2018 Macrophage scavenger receptor SR-AI contributes to the clearance of von Willebrand factor. Haematologica 39 29326120
2003 Germ-line alterations in MSR1 gene and prostate cancer risk. Clinical cancer research : an official journal of the American Association for Cancer Research 36 14614006
2007 Identification of the scavenger receptors SREC-I, Cla-1 (SR-BI), and SR-AI as cellular receptors for Tamm-Horsfall protein. Journal of leukocyte biology 34 17928461
2015 Cyr61 promotes CD204 expression and the migration of macrophages via MEK/ERK pathway in esophageal squamous cell carcinoma. Cancer medicine 33 25620088
2012 Highly upregulated expression of CD36 and MSR1 in circulating monocytes of patients with acute coronary syndromes. The protein journal 33 22763563
2011 CD204 suppresses large heat shock protein-facilitated priming of tumor antigen gp100-specific T cells and chaperone vaccine activity against mouse melanoma. Journal of immunology (Baltimore, Md. : 1950) 32 21832164
2018 CD204-Expressing Tumor-Associated Macrophages Are Associated With Malignant, High-Grade, and Hormone Receptor-Negative Canine Mammary Gland Tumors. Veterinary pathology 31 29343199
2011 A tumor suppressor function of the Msr1 gene in leukemia stem cells of chronic myeloid leukemia. Blood 31 21596859
2003 Adenovirus-mediated gene transfer of a secreted decoy human macrophage scavenger receptor (SR-AI) in LDL receptor knock-out mice. Atherosclerosis 30 12860255
2012 In situ vaccination with CD204 gene-silenced dendritic cell, not unmodified dendritic cell, enhances radiation therapy of prostate cancer. Molecular cancer therapeutics 29 22896667
2010 mamO and mamE genes are essential for magnetosome crystal biomineralization in Magnetospirillum gryphiswaldense MSR-1. Research in microbiology 29 20674739
2007 Class A scavenger receptor (CD204) attenuates hyperoxia-induced lung injury by reducing oxidative stress. The Journal of pathology 29 17370294
2016 Low density of CD204-positive M2-type tumor-associated macrophages in Epstein-Barr virus-associated gastric cancer: a clinicopathologic study with digital image analysis. Human pathology 28 27342912
2019 Characterization of transcriptome profile and clinical features of a novel immunotherapy target CD204 in diffuse glioma. Cancer medicine 27 31140757
2013 Regulation of MSR-1 and CD36 in macrophages by LOX-1 mediated through PPAR-γ. Biochemical and biophysical research communications 27 23333385
2011 Suppression of antigen-specific CD4+ T cell activation by SRA/CD204 through reducing the immunostimulatory capability of antigen-presenting cell. Journal of molecular medicine (Berlin, Germany) 25 22083206
2006 Meta-analysis of association of rare mutations and common sequence variants in the MSR1 gene and prostate cancer risk. The Prostate 25 16425212
2022 Tumour-associated CD204+ microglia/macrophages accumulate in perivascular and perinecrotic niches and correlate with an interleukin-6-enriched inflammatory profile in glioblastoma. Neuropathology and applied neurobiology 24 34713474
2022 MSR1 characterized by chromatin accessibility mediates M2 macrophage polarization to promote gastric cancer progression. International immunopharmacology 24 36095948
2016 Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: Role of CD14 and SR-AI receptors. Nutrition, metabolism, and cardiovascular diseases : NMCD 24 27378395
2014 Circulating CD14+CD204+ cells predict postoperative recurrence in non-small-cell lung cancer patients. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 24 24419414
2008 Characterization of immortalized MARCO and SR-AI/II-deficient murine alveolar macrophage cell lines. Particle and fibre toxicology 24 18452625
2020 Neuroprotective Effect of Phthalide Derivative CD21 against Ischemic Brain Injury:Involvement of MSR1 Mediated DAMP peroxiredoxin1 Clearance and TLR4 Signaling Inhibition. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 22 32291602
2006 Germline mutations of the MSR1 gene in prostate cancer families from Germany. Human mutation 22 16287155
2006 Mutation screening and association study of the candidate prostate cancer susceptibility genes MSR1, PTEN, and KLF6. The Prostate 22 16598737
2018 Development of a simple intensified fermentation strategy for growth of Magnetospirillum gryphiswaldense MSR-1: Physiological responses to changing environmental conditions. New biotechnology 21 29864580
2014 Pattern recognition scavenger receptor A/CD204 regulates airway inflammatory homeostasis following organic dust extract exposures. Journal of immunotoxicology 21 24491035
2014 Role of CD204-positive tumor-associated macrophages in adult T-cell leukemia/lymphoma. Journal of clinical and experimental hematopathology : JCEH 20 24942947
2022 Fatty acids derived from apoptotic chondrocytes fuel macrophages FAO through MSR1 for facilitating BMSCs osteogenic differentiation. Redox biology 19 35525025
2019 The scavenger receptor SCARA1 (CD204) recognizes dead cells through spectrin. The Journal of biological chemistry 19 31653705
2013 Expression patterns of key iron and oxygen metabolism genes during magnetosome formation in Magnetospirillum gryphiswaldense MSR-1. FEMS microbiology letters 19 23937222
2005 Clearance of apoptotic cells is not impaired in mouse embryos deficient in class A scavenger receptor types I and II (CD204). Developmental dynamics : an official publication of the American Association of Anatomists 18 15580571
2020 Identification of Immune-Related Genes MSR1 and TLR7 in Relation to Macrophage and Type-2 T-Helper Cells in Osteosarcoma Tumor Micro-Environments as Anti-metastasis Signatures. Frontiers in molecular biosciences 17 33381518
2017 LPS enhances expression of CD204 through the MAPK/ERK pathway in murine bone marrow macrophages. Atherosclerosis 17 29032172
2016 Transcriptome analysis reveals physiological characteristics required for magnetosome formation in Magnetospirillum gryphiswaldense MSR-1. Environmental microbiology reports 17 27043321
2015 Iron response regulator protein IrrB in Magnetospirillum gryphiswaldense MSR-1 helps control the iron/oxygen balance, oxidative stress tolerance, and magnetosome formation. Applied and environmental microbiology 17 26386052
2010 The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation. Protein & cell 17 21203986
2007 DNA variation in MSR1, RNASEL and E-cadherin genes and prostate cancer in Poland. Urologia internationalis 17 17627168
2004 Mutational analysis of susceptibility genes RNASEL/HPC1, ELAC2/HPC2, and MSR1 in sporadic prostate cancer. Genes, chromosomes & cancer 17 14695991
2018 JNK1 Mediates Lipopolysaccharide-Induced CD14 and SR-AI Expression and Macrophage Foam Cell Formation. Frontiers in physiology 16 29354064
2017 Physiological characteristics of Magnetospirillum gryphiswaldense MSR-1 that control cell growth under high-iron and low-oxygen conditions. Scientific reports 16 28584275
2013 MamX encoded by the mamXY operon is involved in control of magnetosome maturation in Magnetospirillum gryphiswaldense MSR-1. BMC microbiology 16 24020498
2012 Two bifunctional enzymes with ferric reduction ability play complementary roles during magnetosome synthesis in Magnetospirillum gryphiswaldense MSR-1. Journal of bacteriology 16 23243303
2021 Fusion expression of nanobodies specific for the insecticide fipronil on magnetosomes in Magnetospirillum gryphiswaldense MSR-1. Journal of nanobiotechnology 15 33468141
2019 CD204-Positive Tumor-associated Macrophages Relate to Malignant Transformation of Colorectal Adenoma. Anticancer research 15 31177112
2013 The class A scavenger receptor SR-A/CD204 and the class B scavenger receptor CD36 regulate immune functions of macrophages differently. Innate immunity 15 24257313
2007 A novel ferric reductase purified from Magnetospirillum gryphiswaldense MSR-1. Current microbiology 15 17534559
2021 The relationship between CD204 M2-polarized tumour-associated macrophages (TAMs), tumour-infiltrating lymphocytes (TILs), and microglial activation in glioblastoma microenvironment: a novel immune checkpoint receptor target. Discover oncology 13 35201470
2012 Crystallization and preliminary crystallographic analysis of the C-terminal domain of MamM, a magnetosome-associated protein from Magnetospirillum gryphiswaldense MSR-1. Acta crystallographica. Section F, Structural biology and crystallization communications 13 22869124
2007 Disruption of a fur-like gene inhibits magnetosome formation in Magnetospirillum gryphiswaldense MSR-1. Biochemistry. Biokhimiia 13 18205608
2022 Role of macrophage scavenger receptor MSR1 in the progression of non-alcoholic steatohepatitis. Frontiers in immunology 12 36591228
2021 A comprehensive assessment of the biocompatibility of Magnetospirillum gryphiswaldense MSR-1 bacterial magnetosomes in vitro and in vivo. Toxicology 12 34534559
2019 Clinical and transcriptional signatures of human CD204 reveal an applicable marker for the protumor phenotype of tumor-associated macrophages in breast cancer. Aging 12 31799941
2013 Macrophage scavenger receptor 1 (Msr1, SR-A) influences B cell autoimmunity by regulating soluble autoantigen concentration. Journal of immunology (Baltimore, Md. : 1950) 11 23794629
2007 MSR1 variants and the risks of prostate cancer and benign prostatic hyperplasia: a population-based study in China. Carcinogenesis 11 17768178
2020 CD204-positive monocytes and macrophages ameliorate septic shock by suppressing proinflammatory cytokine production in mice. Biochemistry and biophysics reports 10 32793817
2020 CD204-positive macrophages accumulate in breast cancer tumors with high levels of infiltrating lymphocytes and programmed death ligand-1 expression. Oncology letters 10 33262828
2016 Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO. Journal of biomedical science 10 26892079
2011 Effect of overexpression of human SR-AI on oxLDL uptake and apoptosis in 293T cells. International immunopharmacology 10 21782039
2023 Biosynthesis of magnetosome-nanobody complex in Magnetospirillum gryphiswaldense MSR-1 and a magnetosome-nanobody-based enzyme-linked immunosorbent assay for the detection of tetrabromobisphenol A in water. Analytical and bioanalytical chemistry 9 37934249
2022 Expression of Macrophage Scavenger Receptor (MSR1) in Peripheral Blood Cells from Patients with Different Respiratory Diseases: Beyond Monocytes. Journal of clinical medicine 9 35268530