Innate sensing of oxidation-specific epitopes in health and disease

Nature Reviews Immunology

Volumn 16, Issue 8, 2016, Pages 485-497

  Binder, Christoph J ^a,b   Papac Milicevic, Nikolina ^a,b   Witztum, Joseph L ^c  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b ERICH SCHMID INSTITUTE OF MATERIALS SCIENCE   (Austria)

^c UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; OXIDATION SPECIFIC EPITOPE; PATTERN RECOGNITION RECEPTOR; UNCLASSIFIED DRUG;

AGE RELATED MACULAR DEGENERATION; ANTIGEN RECOGNITION; ATHEROSCLEROSIS; CHRONIC INFLAMMATION; HUMAN; INNATE IMMUNITY; LIPID PEROXIDATION; MOLECULAR MECHANICS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW; ANIMAL; CELLULAR IMMUNITY; DISEASE PREDISPOSITION; HOMEOSTASIS; HUMORAL IMMUNITY; IMMUNOLOGY; LIPID METABOLISM; OXIDATION REDUCTION REACTION;

ANIMALS; DISEASE SUSCEPTIBILITY; EPITOPES; HOMEOSTASIS; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; IMMUNITY, INNATE; LIPID METABOLISM; LIPID PEROXIDATION; OXIDATION-REDUCTION; OXIDATIVE STRESS;

EID: 84976273749     PISSN: 14741733     EISSN: 14741741     Source Type: Journal    
DOI: 10.1038/nri.2016.63     Document Type: Review

References (151)

1. Schieber, M., & Chandel, N. S. ROS function in redox signaling and oxidative stress. Curr. Biol. 24, R453-R462 2014
2. Savina, A., et al. NOX2 controls phagosomal pH to regulate antigen processing during crosspresentation by dendritic cells. Cell 126, 205-218 (2006
3. Nathan, C., & Cunningham-Bussel, A. Beyond oxidative stress: an immunologist s guide to reactive oxygen species. Nat. Rev. Immunol. 13, 349-361 (2013
4. Finkel, T., & Holbrook, N. J. Oxidants, oxidative stress and the biology of ageing. Nature 408, 239-247 (2000
5. Klebanoff, S. J. Myeloperoxidase: friend and foe. J. Leukoc. Biol. 77, 598-625 (2005
6. Almyroudis, N. G., et al. NETosis and NADPH oxidase: at the intersection of host defense, inflammation, and injury. Front. Immunol. 4, 45 (2013
7. Bae, Y. S., Oh, H., Rhee, S. G., & Yoo, Y. D. Regulation of reactive oxygen species generation in cell signaling. Mol. Cells 32, 491-509 (2011
8. Esterbauer, H., Schaur, R. J., & Zollner, H. Chemistry and biochemistry of 4 hydroxynonenal, malonaldehyde and related aldehydes. Free Radic. Biol. Med. 11, 81-128 (1991
9. Cyster, J. G., Dang, E. V., Reboldi, A., & Yi, T. 25 Hydroxycholesterols in innate and adaptive immunity. Nat. Rev. Immunol. 14, 731-743 (2014
10. Spann, N. J., & Glass, C. K. Sterols and oxysterols in immune cell function. Nat. Immunol. 14, 893-900 (2013)
11. Bauer, J., et al. Pathophysiology of isoprostanes in the cardiovascular system: implications of isoprostane-mediated thromboxane A2 receptor activation. Br. J. Pharmacol. 171, 3115-3131 (2014
12. Serhan, C. N. Pro-resolving lipid mediators are leads for resolution physiology. Nature 510, 92-101 (2014
13. Rothe, T., et al. 12/15 Lipoxygenase-mediated enzymatic lipid oxidation regulates DC maturation and function. J. Clin. Invest. 125, 1944-1954 (2015
14. Miller, Y. I., et al. Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ. Res. 108, 235-248 (2011
15. Kawamoto, Y., et al. Cyclopentenone prostaglandins as potential inducers of phase II detoxification enzymes. 15 deoxy-?(12,14)-prostaglandin j2 induced expression of glutathione S transferases. J. Biol. Chem. 275, 11291-11299 (2000
16. Clark, S. R., et al. Characterization of platelet aminophospholipid externalization reveals fatty acids as molecular determinants that regulate coagulation. Proc. Natl Acad. Sci. USA 110, 5875-5880 (2013
17. Chang, M. K., et al. Apoptotic cells with oxidation-specific epitopes are immunogenic and proinflammatory. J. Exp. Med. 200, 1359-1370 (2004
18. Chang, M. K., et al. Monoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: evidence that oxidation-specific epitopes mediate macrophage recognition. Proc. Natl Acad. Sci. USA 96, 6353-6358 (1999
19. Chou, M. Y., et al. Oxidation-specific epitopes are important targets of innate immunity. J. Intern. Med. 263, 479-488 (2008
20. Tsiantoulas, D., et al. Circulating microparticles carry oxidation-specific epitopes and are recognized by natural IgM antibodies. J. Lipid. Res. 56, 440-448 (2015
21. Gallucci, S., & Matzinger, P. Danger signals: SOS to the immune system. Curr. Opin. Immunol. 13, 114-119 (2001
22. Chen, G. Y., & Nunez, G. Sterile inflammation: sensing and reacting to damage. Nat. Rev. Immunol. 10, 826-837 (2010
23. Bochkov, V. N., et al. Generation and biological activities of oxidized phospholipids. Antioxid. Redox Signal. 12, 1009-1059 (2010
24. Salomon, R. G. Structural identification and cardiovascular activities of oxidized phospholipids. Circ. Res. 111, 930-946 (2012
25. Harkewicz, R., et al. Cholesteryl ester hydroperoxides are biologically active components of minimally oxidized low density lipoprotein. J. Biol. Chem. 283, 10241-10251 (2008
26. Steinberg, D., & Witztum, J. L. Oxidized low-density lipoprotein and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 30, 2311-2316 (2010
27. O Donnell, V. B., & Murphy, R. C. New families of bioactive oxidized phospholipids generated by immune cells: identification and signaling actions. Blood 120, 1985-1992 (2012
28. Lee, S., et al. Role of phospholipid oxidation products in atherosclerosis. Circ. Res. 111, 778-799 (2012
29. Fadeel, B., Xue, D., & Kagan, V. Programmed cell clearance: molecular regulation of the elimination of apoptotic cell corpses and its role in the resolution of inflammation. Biochem. Biophys. Res. Commun. 396, 7-10 (2010
30. Salomon, R. G., Hong, L., & Hollyfield, J. G. Discovery of carboxyethylpyrroles (CEPs): critical insights into AMD, autism, cancer, and wound healing from basic research on the chemistry of oxidized phospholipids. Chem. Res. Toxicol. 24, 1803-1816 (2011
31. Weismann, D., & Binder, C. J. The innate immune response to products of phospholipid peroxidation. Biochim. Biophys. Acta 1818, 2465-2475 (2012
32. Harnett, W., & Harnett, M. M. Phosphorylcholine: friend or foe of the immune system? Immunol. Today 20, 125-129 (1999
33. West, X. Z., et al. Oxidative stress induces angiogenesis by activating TLR2 with novel endogenous ligands. Nature 467, 972-976 (2010
34. Wang, H., et al. 4 Hydroxy 7 oxo 5 heptenoic acid (HOHA) lactone is a biologically active precursor for the generation of 2-(?a-Carboxyethyl)pyrrole (CEP) derivatives of proteins and ethanolamine phospholipids. Chem. Res. Toxicol. 28, 967-977 (2015
35. Choi, S. H., et al. Polyoxygenated cholesterol ester hydroperoxide activates TLR4 and SYK dependent signaling in macrophages. PLoS ONE 8, e83145 2013
36. Witztum, J. L., & Lichtman, A. H. The influence of innate and adaptive immune responses on atherosclerosis. Annu. Rev. Pathol. 9, 73-102 (2014
37. Greaves, D. R., & Gordon, S. The macrophage scavenger receptor at 30 years of age: current knowledge and future challenges. J. Lipid Res. 50, S282-S286 2009
38. Kunjathoor, V. V., et al. Scavenger receptors class A I/II and CD36 are the principal receptors responsible for the uptake of modified low density lipoprotein leading to lipid loading in macrophages. J. Biol. Chem. 277, 49982-49988 (2002
39. Boullier, A., et al. The binding of oxidized low density lipoprotein to mouse CD36 is mediated in part by oxidized phospholipids that are associated with both the lipid and protein moieties of the lipoprotein. J. Biol. Chem. 275, 9163-9169 (2000
40. Boullier, A., et al. Phosphocholine as a pattern recognition ligand for CD36. J. Lipid Res. 46, 969-976 (2005
41. Li, X. M., Salomon, R. G., Qin, J., & Hazen, S. L. Conformation of an endogenous ligand in a membrane bilayer for the macrophage scavenger receptor CD36. Biochemistry 46, 5009-5017 (2007
42. Greenberg, M. E., et al. The lipid whisker model of the structure of oxidized cell membranes. J. Biol. Chem. 283, 2385-2396 (2008
43. Fadok, V. A., Warner, M. L., Bratton, D. L., & Henson, P. M. CD36 is required for phagocytosis of apoptotic cells by human macrophages that use either a phosphatidylserine receptor or the vitronectin receptor (αvβ3). J. Immunol. 161, 6250-6257 (1998
44. Greenberg, M. E., et al. Oxidized phosphatidylserine- CD36 interactions play an essential role in macrophage-dependent phagocytosis of apoptotic cells. J. Exp. Med. 203, 2613-2625 (2006
45. Gillotte-Taylor, K., Boullier, A., Witztum, J. L., Steinberg, D., & Quehenberger, O. Scavenger receptor class B type I as a receptor for oxidized low density lipoprotein. J. Lipid Res. 42, 1474-1482 (2001
46. Kim, Y. W., et al. Receptor-mediated mechanism controlling tissue levels of bioactive lipid oxidation products. Circ. Res. 117, 321-332 (2015
47. Duryee, M. J., et al. Scavenger receptors on sinusoidal liver endothelial cells are involved in the uptake of aldehyde-modified proteins. Mol. Pharmacol. 68, 1423-1430 (2005
48. Shechter, I., et al. The metabolism of native and malondialdehyde-altered low density lipoproteins by human monocyte-macrophages. J. Lipid Res. 22, 63-71 (1981
49. Besler, C., et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J. Clin. Invest. 121, 2693-2708 (2011
50. Kumano-Kuramochi, M., et al. Identification of 4 hydroxy 2 nonenal-histidine adducts that serve as ligands for human lectin-like oxidized LDL receptor 1. Biochem. J. 442, 171-180 (2012
51. Imai, Y., et al. Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133, 235-249 (2008
52. Kadl, A., et al. Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2. Free Radic. Biol. Med. 51, 1903-1909 (2011
53. Stewart, C. R., et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer. Nat. Immunol. 11, 155-161 (2010
54. Seimon, T. A., et al. Atherogenic lipids and lipoproteins trigger CD36-TLR2 dependent apoptosis in macrophages undergoing endoplasmic reticulum stress. Cell. Metab. 12, 467-482 (2010
55. Saeed, A. M., et al. The oxidative stress product carboxyethylpyrrole potentiates TLR2/TLR1 inflammatory signaling in macrophages. PLoS ONE 9, e106421 (2014
56. Biswas, S., et al. Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE?/? mice and activate platelets via TLR2. Blood http://dx.doi.org/10.1182/blood-2015-08-664300 (2016
57. Gargiulo, S., et al. Relation between TLR4/NF ?B signaling pathway activation by 27 hydroxycholesterol and 4 hydroxynonenal, and atherosclerotic plaque instability. Aging Cell 14, 569-581 (2015
58. Choi, S. H., et al. Lipoprotein accumulation in macrophages via Toll-like receptor 4 dependent fluid phase uptake. Circ. Res. 104, 1355-1363 (2009
59. Bochkov, V. N., et al. Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature 419, 77-81 (2002
60. Bretscher, P., et al. Phospholipid oxidation generates potent anti-inflammatory lipid mediators that mimic structurally related pro-resolving eicosanoids by activating Nrf2. EMBO Mol. Med. 7, 593-607 (2015
61. Litvack, M. L., & Palaniyar, N. Review: soluble innate immune pattern-recognition proteins for clearing dying cells and cellular components: implications on exacerbating or resolving inflammation. Innate Immun. 16, 191-200 (2010
62. Volanakis, J. E., & Kaplan, M. H. Specificity of C reactive protein for choline phosphate residues of pneumococcal C polysaccharide. Proc. Soc. Exp. Biol. Med. 136, 612-614 (1971
63. Volanakis, J. E. Human C reactive protein: expression, structure, and function. Mol. Immunol. 38, 189-197 (2001
64. Verma, S., Szmitko, P. E., & Ridker, P. M. C reactive protein comes of age. Nat. Clin. Pract. Cardiovasc. Med. 2, 29-36 (2005
65. Chang, M. K., Binder, C. J., Torzewski, M., & Witztum, J. L. C reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc. Natl Acad. Sci. USA 99, 13043-13048 (2002
66. Turunen, S. P., et al. Recognition of Porphyromonas gingivalis gingipain epitopes by natural IgM binding to malondialdehyde modified low-density lipoprotein. PLoS ONE 7, e34910 2012
67. Weismann, D., et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 478, 76-81 (2011
68. Zipfel, P. F., & Skerka, C. Complement regulators and inhibitory proteins. Nat. Rev. Immunol. 9, 729-740 (2009
69. Zipfel, P. F., Heinen, S., Jozsi, M., & Skerka, C. Complement and diseases: defective alternative pathway control results in kidney and eye diseases. Mol. Immunol. 43, 97-106 (2006
70. Hyvarinen, S., Uchida, K., Varjosalo, M., Jokela, R., & Jokiranta, T. S. Recognition of malondialdehyde-modified proteins by the C terminus of complement factor H is mediated via the polyanion binding site and impaired by mutations found in atypical hemolytic uremic syndrome. J. Biol. Chem. 289, 4295-4306 (2014)
71. Veneskoski, M., et al. Specific recognition of malondialdehyde and malondialdehyde acetaldehyde adducts on oxidized LDL and apoptotic cells by complement anaphylatoxin C3a. Free Radic. Biol. Med. 51, 834-843 (2011
72. Borisenko, G. G., Iverson, S. L., Ahlberg, S., Kagan, V. E., & Fadeel, B. Milk fat globule epidermal growth factor 8 (MFG E8) binds to oxidized phosphatidylserine: implications for macrophage clearance of apoptotic cells. Cell Death Differ. 11, 943-945 (2004
73. Uderhardt, S., et al 12/15 lipoxygenase orchestrates the clearance of apoptotic cells and maintains immunologic tolerance. Immunity 36 834-846 2012
74. Wan, M., et al. Oxidized but not native cardiolipin has pro-inflammatory effects, which are inhibited by Annexin A5. Atherosclerosis 235, 592-598 (2014
75. Chou, M. Y., et al. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J. Clin. Invest. 119, 1335-1349 (2009
76. Shaw, P. X., et al. Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J. Clin. Invest. 105, 1731-1740 (2000
77. Horkko, S., et al. Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J. Clin. Invest. 103, 117-128 (1999
78. Palinski, W., et al. Cloning of monoclonal autoantibodies to epitopes of oxidized lipoproteins from apolipoprotein E deficient mice. Demonstration of epitopes of oxidized low density lipoprotein in human plasma. J. Clin. Invest. 98, 800-814 (1996
79. Potter, M., & Lieberman, R. Common individual antigenic determinants in five of eight BALB c IgA myeloma proteins that bind phosphoryl choline. J. Exp. Med. 132, 737-751 (1970
80. Briles, D. E., Forman, C., Hudak, S., & Claflin, J. L. Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae. J. Exp. Med. 156, 1177-1185 (1982
81. Amir, S., et al. Peptide mimotopes of malondialdehyde epitopes for clinical applications in cardiovascular disease. J. Lipid Res. 53, 1316-1326 (2012
82. Tuominen, A., et al. A natural antibody to oxidized cardiolipin binds to oxidized low-density lipoprotein, apoptotic cells, and atherosclerotic lesions. Arterioscler. Thromb. Vasc. Biol. 26, 2096-2102 (2006
83. Arandjelovic, S., & Ravichandran, K. S. Phagocytosis of apoptotic cells in homeostasis. Nat. Immunol. 16, 907-917 (2015
84. Poon, I. K., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S. Apoptotic cell clearance: basic biology and therapeutic potential. Nat. Rev. Immunol. 14, 166-180 (2014
85. Ravichandran, K. S. Beginnings of a good apoptotic meal: the find me and eat me signaling pathways. Immunity 35, 445-455 (2011
86. Chen, Y., et al. Regulation of dendritic cells and macrophages by an anti-apoptotic cell natural antibody that suppresses TLR responses and inhibits inflammatory arthritis. J. Immunol. 183, 1346-1359 (2009
87. Chen, Y., Park, Y. B., Patel, E., & Silverman, G. J. IgM antibodies to apoptosis-associated determinants recruit C1q and enhance dendritic cell phagocytosis of apoptotic cells. J. Immunol. 182, 6031-6043 (2009
88. Huber, J., et al. Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions. Arterioscler. Thromb. Vasc. Biol. 22, 101-107 (2002
89. Liu, M. L., Scalia, R., Mehta, J. L., & Williams, K. J. Cholesterol-induced membrane microvesicles as novel carriers of damage-associated molecular patterns: mechanisms of formation, action, and detoxification. Arterioscler. Thromb. Vasc. Biol. 32, 2113-2121 (2012
90. Rautou, P. E., et al. Microparticles, vascular function, and atherothrombosis. Circ. Res. 109, 593-606 (2011
91. Biro, E., et al. Activated complement components and complement activator molecules on the surface of cell-derived microparticles in patients with rheumatoid arthritis and healthy individuals. Ann. Rheum. Dis. 66, 1085-1092 (2007
92. Linkermann, A., Stockwell, B. R., Krautwald, S., & Anders, H. J. Regulated cell death and inflammation: an auto-amplification loop causes organ failure. Nat. Rev. Immunol. 14, 759-767 (2014
93. Duncan, K. G., Bailey, K. R., Kane, J. P., & Schwartz, D. M. Human retinal pigment epithelial cells express scavenger receptors BI and BII. Biochem. Biophys. Res. Commun. 292, 1017-1022 (2002
94. Sparrow, J. R., Ryeom, S. W., Abumrad, N. A., Ibrahimi, A., & Silverstein, R. L. CD36 expression is altered in retinal pigment epithelial cells of the RCS rat. Exp. Eye Res. 64, 45-56 (1997
95. Ryeom, S. W., Silverstein, R. L., Scotto, A., & Sparrow, J. R. Binding of anionic phospholipids to retinal pigment epithelium may be mediated by the scavenger receptor CD36. J. Biol. Chem. 271, 20536-20539 (1996
96. Sun, M., et al. Light-induced oxidation of photoreceptor outer segment phospholipids generates ligands for CD36 mediated phagocytosis by retinal pigment epithelium: a potential mechanism for modulating outer segment phagocytosis under oxidant stress conditions. J. Biol. Chem. 281, 4222-4230 (2006
97. Nandrot, E. F., et al. Essential role for MFG E8 as ligand for αvβ5 integrin in diurnal retinal phagocytosis. Proc. Natl Acad. Sci. USA 104, 12005-12010 (2007
98. Peng, Y., Kowalewski, R., Kim, S., & Elkon, K. B. The role of IgM antibodies in the recognition and clearance of apoptotic cells. Mol. Immunol. 42, 781-787 (2005
99. Taylor, P. R., et al. A hierarchical role for classical pathway complement proteins in the clearance of apoptotic cells in vivo. J. Exp. Med. 192, 359-366 (2000
100. Boes, M., et al. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc. Natl Acad. Sci. USA 97, 1184-1189 (2000
101. Ogden, C. A., Kowalewski, R., Peng, Y., Montenegro, V., & Elkon, K. B. IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo. Autoimmunity 38, 259-264 (2005
102. Wang, G., Li, H., & Firoze Khan, M. Differential oxidative modification of proteins in MRL+/+ and MRL/lpr mice: Increased formation of lipid peroxidation-derived aldehyde-protein adducts may contribute to accelerated onset of autoimmune response. Free Radic. Res. 46, 1472-1481 (2012
103. Gershov, D., Kim, S., Brot, N., & Elkon, K. B. C Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity. J. Exp. Med. 192, 1353-1364 (2000
104. Trouw, L. A., et al. C4b binding protein and factor H compensate for the loss of membrane-bound complement inhibitors to protect apoptotic cells against excessive complement attack. J. Biol. Chem. 282, 28540-28548 (2007
105. Trouw, L. A., Blom, A. M., & Gasque, P. Role of complement and complement regulators in the removal of apoptotic cells. Mol. Immunol. 45, 1199-1207 (2008
106. Amarilyo, G., et al. iC3b opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF ?B-dependent blockade. Eur. J. Immunol. 40, 699-709 (2010
107. Lauer, N., et al. Complement regulation at necrotic cell lesions is impaired by the age-related macular degeneration-associated factor H His402 risk variant. J. Immunol. 187, 4374-4383 (2011
108. Kang, Y. H., Urban, B. C., Sim, R. B., & Kishore, U. Human complement factor H modulates C1q mediated phagocytosis of apoptotic cells. Immunobiology 217, 455-464 (2012
109. Gresham, H. D., et al. Negative regulation of phagocytosis in murine macrophages by the Src kinase family member, Fgr. J. Exp. Med. 191, 515-528 (2000
110. Matt, U., et al. WAVE1 mediates suppression of phagocytosis by phospholipid-derived DAMPs. J. Clin. Invest. 123, 3014-3024 (2013
111. Wyatt, T. A., et al. Malondialdehyde-acetaldehyde-adducted protein inhalation causes lung injury. Alcohol 46, 51-59 (2012
112. Libby, P., Lichtman, A. H., & Hansson, G. K. Immune effector mechanisms implicated in atherosclerosis: from mice to humans. Immunity 38, 1092-1104 (2013
113. Jurgens, G., et al. Immunostaining of human autopsy aortas with antibodies to modified apolipoprotein B and apoprotein(a). Arterioscler. Thromb. 13, 1689-1699 (1993
114. Yla-Herttuala, S., et al. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J. Clin. Invest. 84, 1086-1095 (1989
115. van Dijk, R. A., et al. Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions. J. Lipid Res. 53, 2773-2790 (2012
116. Walton, K. A., et al. Receptors involved in the oxidized 1 palmitoyl 2 arachidonoyl-sn glycero 3 phosphorylcholine-mediated synthesis of interleukin 8. A role for Toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein. J. Biol. Chem. 278, 29661-29666 (2003
117. Mehta, J. L., et al. Deletion of LOX 1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet. Circ. Res. 100, 1634-1642 (2007
118. Mullick, A. E., et al. Increased endothelial expression of Toll-like receptor 2 at sites of disturbed blood flow exacerbates early atherogenic events. J. Exp. Med. 205, 373-383 (2008
119. Moore, K. J., Sheedy, F. J., & Fisher, E. A. Macrophages in atherosclerosis: a dynamic balance. Nat. Rev. Immunol. 13, 709-721 (2013
120. Duewell, P., et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464, 1357-1361 (2010
121. Sheedy, F. J., et al. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat. Immunol. 14, 812-820 (2013
122. Michelsen, K. S., et al. Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E. Proc. Natl Acad. Sci. USA 101, 10679-10684 (2004
123. Ameziane, N., et al. Association of the Toll-like receptor 4 gene Asp299Gly polymorphism with acute coronary events. Arterioscler. Thromb. Vasc. Biol. 23, e61-e64
124. Kiechl, S., et al. Toll-like receptor 4 polymorphisms and atherogenesis. N. Engl. J. Med. 347, 185-192 (2002
125. Tabas, I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat. Rev. Immunol. 10, 36-46 (2010
126. Tsiantoulas, D., Diehl, C. J., Witztum, J. L., & Binder, C. J. B cells and humoral immunity in atherosclerosis. Circ. Res. 114, 1743-1756 (2014
127. Tanigaki, K., et al. Fcγ receptors and ligands and cardiovascular disease. Circ. Res. 116, 368-384 (2015
128. Zacho, J., et al. Genetically elevated C reactive protein and ischemic vascular disease. N. Engl. J. Med. 359, 1897-1908 (2008
129. Binder, C. J., et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat. Med. 9, 736-743 (2003
130. Faria-Neto, J. R., et al. Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E null mice. Atherosclerosis 189, 83-90 (2006
131. Oksjoki, R., et al. Association between complement factor H and proteoglycans in early human coronary atherosclerotic lesions: implications for local regulation of complement activation. Arterioscler. Thromb. Vasc. Biol. 23, 630-636 (2003)
132. Sofat, R., et al. Genetic variation in complement factor H and risk of coronary heart disease: eight new studies and a meta-analysis of around 48,000 individuals. Atherosclerosis 213, 184-190 (2010
133. Walenbergh, S. M., Koek, G. H., Bieghs, V., & Shiri-Sverdlov, R. Non-alcoholic steatohepatitis: the role of oxidized low-density lipoproteins. J. Hepatol. 58, 801-810 (2013
134. Bieghs, V., et al. Internalization of modified lipids by CD36 and SR A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells. PLoS ONE 7, e34378 2012
135. Bieghs, V., et al. Specific immunization strategies against oxidized low-density lipoprotein: a novel way to reduce nonalcoholic steatohepatitis in mice. Hepatology 56, 894-903 (2012
136. Gruber, S., et al. Sialic acid-binding immunoglobulin-like lectin G promotes atherosclerosis and liver inflammation by suppressing the protective functions of B-1 cells. Cell Rep. 14, 2348-2361 (2016
137. McHarg, S., Clark, S. J., Day, A. J., & Bishop, P. N. Age-related macular degeneration and the role of the complement system. Mol. Immunol. 67, 43-50 (2015
138. Handa, J. T. How does the macula protect itself from oxidative stress? Mol. Aspects Med. 33, 418-435 (2012
139. Doyle, S. L., et al. NLRP3 has a protective role in age-related macular degeneration through the induction of IL 18 by drusen components. Nat. Med. 18, 791-798 (2012
140. Haines, J. L., et al. Complement factor H variant increases the risk of age-related macular degeneration. Science 308, 419-421 (2005
141. Edwards, A. O., et al. Complement factor H polymorphism and age-related macular degeneration. Science 308, 421-424 (2005
142. Aredo, B., et al. A chimeric Cfh transgene leads to increased retinal oxidative stress, inflammation, and accumulation of activated subretinal microglia in mice. Invest. Ophthalmol. Vis. Sci. 56, 3427-3440 (2015
143. Kris-Etherton, P. M., et al. Antioxidant vitamin supplements and cardiovascular disease. Circulation 110, 637-641 (2004
144. Niki, E., Yoshida, Y., Saito, Y., & Noguchi, N. Lipid peroxidation: mechanisms, inhibition, and biological effects. Biochem. Biophys. Res. Commun. 338, 668-676 (2005
145. Thomas, C. P., & O Donnell, V. B. Oxidized phospholipid signaling in immune cells. Curr. Opin. Pharmacol. 12, 471-477 (2012
146. Nicholls, S. J., & Hazen, S. L. Myeloperoxidase, modified lipoproteins, and atherogenesis. J. Lipid Res. 50, S346-S351 2009
147. Mauerhofer, C., Philippova, M., Oskolkova, O. V., & Bochkov, V. N. Mol. Aspects Med. 49, 78-90 (2016
148. Krieg, P., et al. Aloxe3 knockout mice reveal a function of epidermal lipoxygenase 3 as hepoxilin synthase and its pivotal role in barrier formation. J. Invest. Dermatol. 133, 172-180 (2013
149. Chiang, N., Arita, M., & Serhan, C. N. Anti-inflammatory circuitry: lipoxin, aspirin-triggered lipoxins and their receptor ALX. Prostaglandins Leukot. Essent. Fatty Acids 73, 163-177 (2005
150. Latz, E., Xiao, T. S., & Stutz, A. Activation and regulation of the inflammasomes. Nat. Rev. Immunol. 13, 397-411 (2013
151. Marnell, L., Mold, C., & Du Clos, T. W. C reactive protein: ligands, receptors and role in inflammation. Clin. Immunol. 117, 104-111 (2005)