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Gene Review

Msr1  -  macrophage scavenger receptor 1

Mus musculus

Synonyms: MRS-A, MSR, MSR-A, Macrophage acetylated LDL receptor I and II, Macrophage scavenger receptor types I and II, ...
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Disease relevance of Msr1


Psychiatry related information on Msr1


High impact information on Msr1


Chemical compound and disease context of Msr1


Biological context of Msr1

  • Whereas MARCO was involved in opsonin-independent phagocytosis in CpG-ODN-pretreated but not in IL-4-pretreated J774 cells, anti-SR-A Abs inhibited particle uptake in untreated and IL-4-pretreated but not in CpG-ODN-pretreated cells [9].
  • Our current results indicate and suggest a model for MSR ligands differentially modulating specific PK signal transduction pathways, which regulate atherogenesis-related inflammatory cytokines TNF and IL-1 [10].
  • Whereas blockage of lysyl residues on apoB-100 of oxLDL by lipid peroxidation products appears to be critical for recognition by the scavenger receptor class A (SR-A), modification of the lipid moiety has been suggested to be responsible for recognition by the scavenger class B receptor, CD36 [11].
  • Macrophages lacking JNK2 displayed suppressed foam cell formation caused by defective uptake and degradation of modified lipoproteins and showed increased amounts of the modified lipoprotein-binding and -internalizing scavenger receptor A (SR-A), whose phosphorylation was markedly decreased [2].
  • As evidence, FC loading by non-SRA mechanisms activates p38 and CHOP, but not apoptosis unless the SRA is engaged [12].

Anatomical context of Msr1


Associations of Msr1 with chemical compounds

  • These data show that alternative lipid uptake mechanisms may contribute to macrophage cholesterol ester accumulation in vivo and suggest that the roles of SR-A and CD36 as proatherosclerotic mediators of modified LDL uptake in vivo need to be reassessed [13].
  • Extensively oxidized LDL and LDL modified by exposure to fatty acid peroxidation products were efficient competitors for the uptake of labeled oxidized LDL by SR-AI/II-deficient Kupffer cells, while acetyl LDL and malondialdehyde-modified LDL were relatively poor competitors [16].
  • Following NB-DNJ treatment SR-A became Endo H-sensitive, consistent with inhibition of N-glycan processing [7].
  • Glycolaldehyde, a reactive intermediate for advanced glycation end products, plays an important role in the generation of an active ligand for the macrophage scavenger receptor [17].
  • When EDTA was added to chelate divalent cations, the SR-A mediated 90 and 95% of the macrophage adhesion without and with serum, respectively [18].

Physical interactions of Msr1


Regulatory relationships of Msr1


Other interactions of Msr1

  • In this study, Apoe-/- mice lacking SR-A or CD36, backcrossed into the C57BL/6 strain for 7 generations, were fed an atherogenic diet for 8 weeks [13].
  • Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO [9].
  • After 4 or 12 weeks of a high-fat diet, the sizes of atherosclerotic lesions in MSR-A/LDLR double knockout mice were significantly reduced (p < 0.05) compared with those in LDLR single knockout mice [23].
  • It also suppressed expression of the 2 major scavenger receptors (scavenger receptor-A [SR-A] and CD36), in part by inhibiting IL-6, and inhibited macrophage foam cell formation [24].
  • The macrophage class A scavenger receptors, macrophage receptor with a collagenous structure (MARCO) and type I/II class A scavenger receptor (SR-AI/II), share structural features and roles in host defense, but little is known about their regulation and signaling properties [9].

Analytical, diagnostic and therapeutic context of Msr1


  1. A quantitative trait loci analysis to map genes involved in lipopolysaccharide-induced inflammatory response: identification of macrophage scavenger receptor 1 as a candidate gene. Fulton, W.B., Reeves, R.H., Takeya, M., De Maio, A. J. Immunol. (2006) [Pubmed]
  2. Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis. Ricci, R., Sumara, G., Sumara, I., Rozenberg, I., Kurrer, M., Akhmedov, A., Hersberger, M., Eriksson, U., Eberli, F.R., Becher, B., Borén, J., Chen, M., Cybulsky, M.I., Moore, K.J., Freeman, M.W., Wagner, E.F., Matter, C.M., Lüscher, T.F. Science (2004) [Pubmed]
  3. A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Suzuki, H., Kurihara, Y., Takeya, M., Kamada, N., Kataoka, M., Jishage, K., Ueda, O., Sakaguchi, H., Higashi, T., Suzuki, T., Takashima, Y., Kawabe, Y., Cynshi, O., Wada, Y., Honda, M., Kurihara, H., Aburatani, H., Doi, T., Matsumoto, A., Azuma, S., Noda, T., Toyoda, Y., Itakura, H., Yazaki, Y., Kodama, T. Nature (1997) [Pubmed]
  4. Protection from lethal gram-positive infection by macrophage scavenger receptor-dependent phagocytosis. Thomas, C.A., Li, Y., Kodama, T., Suzuki, H., Silverstein, S.C., El Khoury, J. J. Exp. Med. (2000) [Pubmed]
  5. Scavenger receptors in neurobiology and neuropathology: their role on microglia and other cells of the nervous system. Husemann, J., Loike, J.D., Anankov, R., Febbraio, M., Silverstein, S.C. Glia (2002) [Pubmed]
  6. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Moore, K.J., Rosen, E.D., Fitzgerald, M.L., Randow, F., Andersson, L.P., Altshuler, D., Milstone, D.S., Mortensen, R.M., Spiegelman, B.M., Freeman, M.W. Nat. Med. (2001) [Pubmed]
  7. Inhibition of alpha-glucosidases I and II increases the cell surface expression of functional class A macrophage scavenger receptor (SR-A) by extending its half-life. Tian, G., Wilcockson, D., Perry, V.H., Rudd, P.M., Dwek, R.A., Platt, F.M., Platt, N. J. Biol. Chem. (2004) [Pubmed]
  8. Successful generation of peripheral neuropathy with onion-bulb formation in the macrophage scavenger receptor classA knockout mouse treated with isoniazid. Naba, I., Yoshikawa, H., Sakoda, S., Itabe, H., Suzuki, H., Kodama, T., Yanagihara, T. Neurosci. Lett. (2000) [Pubmed]
  9. Disparate regulation and function of the class A scavenger receptors SR-AI/II and MARCO. Józefowski, S., Arredouani, M., Sulahian, T., Kobzik, L. J. Immunol. (2005) [Pubmed]
  10. Ligands of macrophage scavenger receptor induce cytokine expression via differential modulation of protein kinase signaling pathways. Hsu, H.Y., Chiu, S.L., Wen, M.H., Chen, K.Y., Hua, K.F. J. Biol. Chem. (2001) [Pubmed]
  11. Phospholipids in oxidized LDL not adducted to apoB are recognized by the CD36 scavenger receptor. Podrez, E.A., Hoppe, G., O'Neil, J., Hoff, H.F. Free Radic. Biol. Med. (2003) [Pubmed]
  12. Cholesterol-induced macrophage apoptosis requires ER stress pathways and engagement of the type A scavenger receptor. Devries-Seimon, T., Li, Y., Yao, P.M., Stone, E., Wang, Y., Davis, R.J., Flavell, R., Tabas, I. J. Cell Biol. (2005) [Pubmed]
  13. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. Moore, K.J., Kunjathoor, V.V., Koehn, S.L., Manning, J.J., Tseng, A.A., Silver, J.M., McKee, M., Freeman, M.W. J. Clin. Invest. (2005) [Pubmed]
  14. Group V secretory phospholipase A2-modified low density lipoprotein promotes foam cell formation by a SR-A- and CD36-independent process that involves cellular proteoglycans. Boyanovsky, B.B., van der Westhuyzen, D.R., Webb, N.R. J. Biol. Chem. (2005) [Pubmed]
  15. Identification of a small-molecule, nonpeptide macrophage scavenger receptor antagonist. Lysko, P.G., Weinstock, J., Webb, C.L., Brawner, M.E., Elshourbagy, N.A. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  16. Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene. Ling, W., Lougheed, M., Suzuki, H., Buchan, A., Kodama, T., Steinbrecher, U.P. J. Clin. Invest. (1997) [Pubmed]
  17. Glycolaldehyde, a reactive intermediate for advanced glycation end products, plays an important role in the generation of an active ligand for the macrophage scavenger receptor. Nagai, R., Matsumoto, K., Ling, X., Suzuki, H., Araki, T., Horiuchi, S. Diabetes (2000) [Pubmed]
  18. The class A scavenger receptor binds to proteoglycans and mediates adhesion of macrophages to the extracellular matrix. Santiago-García, J., Kodama, T., Pitas, R.E. J. Biol. Chem. (2003) [Pubmed]
  19. Scavenger receptor expressed by endothelial cells I (SREC-I) mediates the uptake of acetylated low density lipoproteins by macrophages stimulated with lipopolysaccharide. Tamura, Y., Osuga, J., Adachi, H., Tozawa, R., Takanezawa, Y., Ohashi, K., Yahagi, N., Sekiya, M., Okazaki, H., Tomita, S., Iizuka, Y., Koizumi, H., Inaba, T., Yagyu, H., Kamada, N., Suzuki, H., Shimano, H., Kadowaki, T., Tsujimoto, M., Arai, H., Yamada, N., Ishibashi, S. J. Biol. Chem. (2004) [Pubmed]
  20. Scavenger receptor A mediates H2O2 production and suppression of IL-12 release in murine macrophages. Józefowski, S., Kobzik, L. J. Leukoc. Biol. (2004) [Pubmed]
  21. Inactivation of macrophage scavenger receptor class B type I promotes atherosclerotic lesion development in apolipoprotein E-deficient mice. Zhang, W., Yancey, P.G., Su, Y.R., Babaev, V.R., Zhang, Y., Fazio, S., Linton, M.F. Circulation (2003) [Pubmed]
  22. Non-PKC DAG/phorbol-ester receptor(s) inhibit complement receptor-3 and nPKC inhibit scavenger receptor-AI/II-mediated myelin phagocytosis but cPKC, PI3k, and PLCgamma activate myelin phagocytosis by both. Cohen, G., Makranz, C., Spira, M., Kodama, T., Reichert, F., Rotshenker, S. Glia (2006) [Pubmed]
  23. Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice. Sakaguchi, H., Takeya, M., Suzuki, H., Hakamata, H., Kodama, T., Horiuchi, S., Gordon, S., van der Laan, L.J., Kraal, G., Ishibashi, S., Kitamura, N., Takahashi, K. Lab. Invest. (1998) [Pubmed]
  24. Synthetic retinoid Am80 reduces scavenger receptor expression and atherosclerosis in mice by inhibiting IL-6. Takeda, N., Manabe, I., Shindo, T., Iwata, H., Iimuro, S., Kagechika, H., Shudo, K., Nagai, R. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  25. Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Fraser, I., Hughes, D., Gordon, S. Nature (1993) [Pubmed]
  26. Role of macrophage scavenger receptors in response to Listeria monocytogenes infection in mice. Ishiguro, T., Naito, M., Yamamoto, T., Hasegawa, G., Gejyo, F., Mitsuyama, M., Suzuki, H., Kodama, T. Am. J. Pathol. (2001) [Pubmed]
  27. Role of macrophage scavenger receptors in hepatic granuloma formation in mice. Hagiwara, S.I., Takeya, M., Suzuki, H., Kodama, T., van der Laan, L.J., Kraal, G., Kitamura, N., Takahashi, K. Am. J. Pathol. (1999) [Pubmed]
  28. Scavenger receptors on sinusoidal liver endothelial cells are involved in the uptake of aldehyde-modified proteins. Duryee, M.J., Freeman, T.L., Willis, M.S., Hunter, C.D., Hamilton, B.C., Suzuki, H., Tuma, D.J., Klassen, L.W., Thiele, G.M. Mol. Pharmacol. (2005) [Pubmed]
  29. Polymorphism of class A scavenger receptors in C57BL/6 mice. Daugherty, A., Whitman, S.C., Block, A.E., Rateri, D.L. J. Lipid Res. (2000) [Pubmed]
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