Complement factor H binds malondialdehyde epitopes and protects from oxidative stress
Open accessAbstract
Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Oxidative stress adducts and components of the complement system accumulate in drusen and sub-RPE deposits of patients with AMD.
“Oxidative stress adducts and components of the complement system have been found to accumulate in drusen and sub-RPE deposits of patients with AMD (Weismann et al., 2011; Shaw et al., 2012), and mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD (Imamura et al., 2006; Justilien et al., 2007; Hollyfield et al., 2”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Weismann et al., 2011
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes
Esterbauer, H., Schaur, R. J., & Zollner, H. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90192-6 · Cited by 6,672 · see citing works
Complement factor H polymorphism in age-related macular degeneration
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., et al. (2005) · Science · doi:10.1126/science.1109557 · Cited by 4,492 · see citing works
Complement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449 · see citing works
Complement factor H variant increases the risk of age-related macular degeneration
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., et al. (2005) · Science · doi:10.1126/science.1110359 · Cited by 2,424 · see citing works
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501536102 · Cited by 1,961 · see citing works
A blast from the past: clearance of apoptotic cells regulates immune responses
Savill, J., Dransfield, I., Gregory, C. D., & Haslett, C. (2002) · Nature reviews. Immunology · doi:10.1038/nri957 · Cited by 1,574 · see citing works
Age-related macular degeneration
Jager, R. D., Mieler, W. F., & Miller, J. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0801537 · Cited by 1,379 · see citing works
Complement regulators and inhibitory proteins
Zipfel, P. F., & Skerka, C. (2009) · Nature reviews. Immunology · doi:10.1038/nri2620 · Cited by 1,268 · see citing works
Age-related macular degeneration
de Jong, P. T. V. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmra062326 · Cited by 787 · see citing works
Age-related Macular Degeneration Histopathologic Studies
Green, W. R., & Enger, C. (1993) · Ophthalmology · doi:10.1016/s0161-6420(93)31466-1 · Cited by 757 · see citing works
Binder, C. J., Hörkkö, S., Dewan, A. K., Chang, M.-K., Kieu, E., Goodyear, C. S., Shaw, P. X., Palinski, W., Witztum, J. L., & Silverman, G. J. (2003) · Nature Medicine · doi:10.1038/nm876 · Cited by 735 · see citing works
Oxidative damage-induced inflammation initiates age-related macular degeneration
Hollyfield, J. G., Bonilha, V. L., Rayborn, M. E., Yang, X., Shadrach, K. G., Lu, L., Ufret, R. L., Salomon, R. G., & Perez, V. L. (2008) · Nature Medicine · doi:10.1038/nm1709 · Cited by 710 · see citing works
Miller, Y. I., Choi, S.-H., Wiesner, P., Fang, L., Harkewicz, R., Hartvigsen, K., Boullier, A., Gonen, A., Diehl, C. J., Que, X., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.223875 · Cited by 654 · see citing works
Innate and acquired immunity in atherogenesis
Binder, C. J., Chang, M.-K., Shaw, P. X., Miller, Y. I., Hartvigsen, K., Dewan, A. K., & Witztum, J. L. (2002) · Nature Medicine · doi:10.1038/nm1102-1218 · Cited by 642 · see citing works
Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans
Chou, M.-Y., Fogelstrand, L., Hartvigsen, K., Hansen, L. F., Woelkers, D., Shaw, P. X., Choi, J., Perkmann, T., Bäckhed, F., Miller, Y. I., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36800 · Cited by 468 · see citing works
Hughes, A. E., Orr, N., Esfandiary, H., Diaz-Torres, M., Goodship, T., & Chakravarthy, U. (2006) · Nature Genetics · doi:10.1038/ng1890 · Cited by 467 · see citing works
Chang, M.-K., Bergmark, C., Laurila, A., Hörkkö, S., Han, K., Friedman, P., Dennis, E. A., & Witztum, J. L. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.11.6353 · Cited by 456 · see citing works
Meri, S., & Pangburn, M. K. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.10.3982 · Cited by 413 · see citing works
Systemic Complement Activation in Age-Related Macular Degeneration
Scholl, H. P. N., Issa, P. C., Walier, M., Janzer, S., Pollok‐Kopp, B., Börncke, F., Fritsche, L. G., Chong, V. N., Fimmers, R., Wienker, T. F., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002593 · Cited by 366 · see citing works
Apoptotic Cells with Oxidation-specific Epitopes Are Immunogenic and Proinflammatory
Chang, M.-K., Binder, C. J., Miller, Y. I., Subbanagounder, G., Silverman, G. J., Berliner, J. A., & Witztum, J. L. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031763 · Cited by 334 · see citing works
Factor H family proteins and human diseases
Józsi, M., & Zipfel, P. F. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.04.008 · Cited by 254 · see citing works
Schütt, F., Bergmann, M., Holz, F. G., & Kopitz, J. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.03-0172 · Cited by 241 · see citing works
Thakkinstian, A., Han, P., McEvoy, M., Smith, W. T., Hoh, J. J., Magnússon, K. P., Zhang, K., & Attia, J. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl220 · Cited by 224 · see citing works
Clark, S. J., Higman, V. A., Mulloy, B., Perkins, S. J., Lea, S. M., Sim, R. B., & Day, A. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605083200 · Cited by 185 · see citing works
Shechter, I., Fogelman, A. M., Haberland, M. E., Seager, J., Hokom, M. M., & Edwards, P. A. (1981) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)34741-6 · Cited by 183 · see citing works
Oxidation‐specific epitopes are important targets of innate immunity
Chou, M. ‐., Hartvigsen, K., Hansen, L. F., Fogelstrand, L., Shaw, P. X., Boullier, A., Binder, C. J., & Witztum, J. L. (2008) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2008.01968.x · Cited by 179 · see citing works
Enhancement of macrophage phagocytosis upon iC3b deposition on apoptotic cells
Takizawa, F., Tsuji, S., & Nagasawa, S. (1996) · FEBS Letters · doi:10.1016/s0014-5793(96)01197-0 · Cited by 165 · see citing works
Sun, M., Finnemann, S. C., Febbraio, M., Shan, L., Annangudi, S. P., Podrez, E. A., Hoppe, G., Darrow, R., Organisciak, D. T., Salomon, R. G., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m509769200 · Cited by 165 · see citing works
Trouw, L. A., Bengtsson, A. A., Gelderman, K. A., Dahlbäck, B., Sturfelt, G. K., & Blom, A. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704354200 · Cited by 137 · see citing works
Mihlan, M., Stippa, S., Józsi, M., & Zipfel, P. F. (2009) · Cell Death and Differentiation · doi:10.1038/cdd.2009.103 · Cited by 133 · see citing works
Suzuki, M., Kamei, M., Itabe, H., Yoneda, K., Bando, H., Kume, N., & Tano, Y. (2007) · PubMed Central · Cited by 127 · see citing works
Kaemmerer, E., Schütt, F., Krohne, T. U., Holz, F. G., & Kopitz, J. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0549 · Cited by 122 · see citing works
Higgins, G. T., Wang, J. H., Dockery, P., Cleary, P. E., & Redmond, H. P. (2003) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.02-0742 · Cited by 109 · see citing works
Proinflammatory Effects of Advanced Lipoxidation End Products in Monocytes
Shanmugam, N., Figarola, J. L., Li, Y., Swiderski, P. M., Rahbar, S., & Natarajan, R. D. (2007) · Diabetes · doi:10.2337/db07-1204 · Cited by 86 · see citing works
Annexin-II, DNA, and Histones Serve as Factor H Ligands on the Surface of Apoptotic Cells
Leffler, J., Herbert, A. P., Norstrøm, E. A., Schmidt, C. Q., Barlow, P. N., Blom, A. M., & Martin, M. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.045427 · Cited by 83 · see citing works
The Role of Complement Factor H in Age-related Macular Degeneration: A Review
Donoso, L. A., Vrabec, T. R., & Kuivaniemi, H. (2010) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2009.11.001 · Cited by 81 · see citing works
Interleukin-8 promoter polymorphism -251A/T is a risk factor for age-related macular degeneration
Goverdhan, S. V., Ennis, S., Hannan, S. R., Madhusudhana, K. C., Cree, A. J., Luff, A. J., & Lotery, A. J. (2008) · British Journal of Ophthalmology · doi:10.1136/bjo.2007.123190 · Cited by 79 · see citing works
Amarilyo, G., Verbovetski, I., Atallah, M., Grau, A., Wiser, G., Gill, O., Ben‐Neriah, Y., & Mevorach, D. (2009) · European Journal of Immunology · doi:10.1002/eji.200838951 · Cited by 67 · see citing works
The clearance of apoptotic cells by complement
Flierman, R., & Daha, M. R. (2006) · Immunobiology · doi:10.1016/j.imbio.2006.11.005 · Cited by 64 · see citing works
Xu, D., Thiele, G. M., Kearley, M. L., Haugen, M. D., Klassen, L. W., Sorrell, M. F., & Tuma, D. J. (1997) · Chemical Research in Toxicology · doi:10.1021/tx970069t · Cited by 58 · see citing works
Thiele, G. M., Duryee, M. J., Willis, M. S., Sorrell, M. F., Freeman, T. L., Tuma, D. J., & Klassen, L. W. (2004) · Comparative Hepatology · doi:10.1186/1476-5926-2-s1-s25 · Cited by 43 · see citing works
Sofat, R., Casas, J. P., Meena Kumari, B., Talmud, P. J., Ireland, H., Mika Kivimaki, B., Marmot, M. G., Hughes, A. D., Thom, S., Ebrahim, S. B. J., et al. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.07.021 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ayala, A., Muñoz, M., & Argüelles, S. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/360438 · Cited by 6,557 · see citing works
“adducts with FH can block both the uptake ofMDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice [184]; MDA adducts or MAA adducts can promote binding of complement; (iii) anaphylatoxin C3a (proinflammatory complement components) with oxidatively modified low-density lipoprotein…”
BackgroundComplement System Part I – Molecular Mechanisms of Activation and Regulation
Merle, N. S., Church, S. E., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00262 · Cited by 1,620 · see citing works
“Y402H binds more weakly to MDA and oxidized phospholipids expressed on retinal pigment epithelium compared to the non-mutated protein (198, 200).”
BackgroundComplement System Part II: Role in Immunity
Merle, N. S., Noé, R., Halbwachs‐Mecarelli, L., Frémeaux‐Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00257 · Cited by 1,054 · see citing works
“At risk, FH variant H402 has a weaker capacity to interact with oxidized lipids and malondialdehyde in the drusen, thus allowing constant background complement activation, leading to retinal epithelial cells damage and macrophages activation (249, 250).”
BackgroundBhutto, I. A., & Lutty, G. A. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.04.005 · Cited by 1,005 · see citing works
“Weismann and associates have demonstrated that CFH binds malondialdehyde epitopes and protects against oxidative stress (Weismann et al., 2011).”
BackgroundAge-related macular degeneration
Fleckenstein, M., Keenan, T. D. L., Guymer, R. H., Chakravarthy, U., Schmitz-Valckenberg, S., Klaver, C. C. W., Wong, W. T., & Chew, E. Y. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00265-2 · Cited by 1,051 · see citing works
The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K. B., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 814 · see citing works
“The Binder lab, with our collaboration, showed that CFH, mediated through SCR7 and SCR20, binds to MDA, which is contained in oxidized LDL (Weismann et al., 2011).”
BackgroundInfluentialInflammation and its role in age-related macular degeneration
Kauppinen, A., Paterno, J. J., Błasiak, J., Salminen, A., & Kaarniranta, K. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2147-8 · Cited by 660 · see citing works
“MDA is common lipid peroxidation product that forms protein adducts capable of inducing inflammation and RPE damage [114, 115].”
BackgroundImmunology of age-related macular degeneration
Ambati, J., Atkinson, J. P., & Gelfand, B. D. (2013) · Nature reviews. Immunology · doi:10.1038/nri3459 · Cited by 591 · see citing works
Complement in disease: a defence system turning offensive
Ricklin, D., Reis, E. S., & Lambris, J. D. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.70 · Cited by 558 · see citing works
Retinal microglia: Just bystander or target for therapy?
Karlstetter, M., Scholz, R., Rutar, M., Wong, W. T., Provis, J. M., & Langmann, T. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.11.004 · Cited by 549 · see citing works
Complement in Immune and Inflammatory Disorders: Pathophysiological Mechanisms
Ricklin, D., & Lambris, J. D. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203487 · Cited by 480 · see citing works
“Although questions about disease triggers and the role of systemic versus locally produced complement remain controversial (36), a recent study suggested a contribution of the oxidative stress adduct malondialdehyde as initiator and provided a functional explanation about the disease correlation of the FH Y402H polymo…”
BackgroundInnate sensing of oxidation-specific epitopes in health and disease
Binder, C. J., Papac-Milicevic, N., & Witztum, J. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.63 · Cited by 403 · see citing works
Self-citationHolz, F. G., Strauss, E. C., Schmitz-Valckenberg, S., & Campagne, M. V. L. (2014) · Ophthalmology · doi:10.1016/j.ophtha.2013.11.023 · Cited by 404 · see citing works
Animal models of age related macular degeneration
Pennesi, M. E., Neuringer, M., & Courtney, R. J. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.06.003 · Cited by 391 · see citing works
“For example, the Y402H polymorphism in complement factor H results in a reduced ability of this protein to bind to malondialdehyde, a product of lipid peroxidation which is present in AMD (Weismann et al., 2011).”
BackgroundMechanisms of age‐related macular degeneration and therapeutic opportunities
van Lookeren Campagne, M., LeCouter, J., Yaspan, B. L., & Ye, W. (2014) · The Journal of Pathology · doi:10.1002/path.4266 · Cited by 382 · see citing works
“Of interest, the CFH polymorphism Y402, which is strongly associated with AMD risk, markedly reduces the ability of CFH to bind to MDA [89], providing mechanistic insight into the causal genetic link.”
BackgroundComplement activation, regulation, and molecular basis for complement‐related diseases
Bajic, G., Degn, S. E., Thiel, S., & Andersen, G. R. (2015) · The EMBO Journal · doi:10.15252/embj.201591881 · Cited by 374 · see citing works
“In contrast, the polymorphism Y402H markedly reduced the ability of FH to bind MDA, indicating a causal link to disease etiology (Weismann et al , 2011).”
Risk factors and biomarkers of age-related macular degeneration
Lambert, N. G., Elshelmani, H., Singh, M. K., Mansergh, F. C., Wride, M. A., Padilla, M., Keegan, D., Hogg, R. E., & Ambati, B. K. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.04.003 · Cited by 352 · see citing works
“Increased levels of MDA provide one probable mechanism responsible for RPE cell death (Klein et al., 2013; Weismann et al., 2011).”
Atypical Hemolytic Uremic Syndrome
Kavanagh, D., Goodship, T. H. J., & Richards, A. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2013.08.003 · Cited by 350 · see citing works
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
Yin, C., Ackermann, S., Ma, Z., Mohanta, S. K., Zhang, C., Li, Y., Nietzsche, S., Westermann, M., Peng, L., Hu, D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0336-8 · Cited by 305 · see citing works
A guide to complement biology, pathology and therapeutic opportunity
Mastellos, D. C., Hajishengallis, G., & Lambris, J. D. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00926-1 · Cited by 325 · see citing works
“While the relative contribution of systemic complement stores versus local complement biosynthesis in the retina is still greatly debated, there is evidence for the contribution of both local and systemic mediators to AMD pathogenesis 199 , likely fuelled by an impaired blood–retina barrier allowing for ‘leakage’ of s…”
InfluentialOphthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma
Zhang, K., Zhang, L., & Weinreb, R. N. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3745 · Cited by 316 · see citing works
Riboflavin as a photosensitizer. Effects on human health and food quality
Cardoso, D. R., Libardi, S. H., & Skibsted, L. H. (2012) · Food & Function · doi:10.1039/c2fo10246c · Cited by 317 · see citing works
B Cells and Humoral Immunity in Atherosclerosis
Tsiantoulas, D., Diehl, C. J., Witztum, J. L., & Binder, C. J. (2014) · Circulation Research · doi:10.1161/circresaha.113.301145 · Cited by 297 · see citing works
Sethi, S. M., Fervenza, F. C., Zhang, Y., Zand, L., Vrana, J. A., Nasr, S. H., Theis, J. D., Doǧan, A., & Smith, R. J. (2012) · Kidney International · doi:10.1038/ki.2012.212 · Cited by 297 · see citing works
“These polymorphisms lead to increased baseline AP activity even in normal controls, and studies comparing the H402 and Y402 variants of Factor H have shown that the former is associated with poorer AP control secondary to decreased binding to both endothelial cells and lipid peroxidation products like malondialdehyde,…”
ResultRPE necroptosis in response to oxidative stress and in AMD
Hanus, J., Anderson, C. A., & Wang, S. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.09.002 · Cited by 286 · see citing works
Handa, J. T., Rickman, C. B., Dick, A. D., Gorin, M. B., Miller, J. W., Toth, C. A., Ueffing, M., Zarbin, M. A., & Farrer, L. A. (2019) · Nature Communications · doi:10.1038/s41467-019-11262-1 · Cited by 280 · see citing works
Cholesterol in the retina: The best is yet to come
Pikuleva, I. A., & Curcio, C. A. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.03.002 · Cited by 282 · see citing works
Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging
Rickman, C. B., Farsiu, S., Toth, C. A., & Klingeborn, M. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12757 · Cited by 285 · see citing works
“Recently, a study has shown that CFH may neutralize the pro-inflammatory effects of malondialdehyde (MDA)-induced inflammation in an AMD-risk associated manner.(82) This study suggests that CFH also functions to attenuate oxidative stress insults leading to AMD, which may explain why clinical trials using complement i…”
BackgroundThe Influence of Innate and Adaptive Immune Responses on Atherosclerosis
Witztum, J. L., & Lichtman, A. H. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163936 · Cited by 277 · see citing works
“CFH is the major plasma protein that binds MDA-modified protein (36).”
BackgroundInfluentialComplement factor H related proteins (CFHRs)
Skerka, C., Chen, Q., Frémeaux‐Bacchi, V., & Roumenina, L. T. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.06.001 · Cited by 266 · see citing works
“and toperoxidized lipids ondead cells combinedwith reducedantiinflammatory functions by factor H (Weismann et al., 2011).”
BackgroundWilleit, P., Skroblin, P., Moschen, A. R., Yin, X., Kaudewitz, D., Zampetaki, A., Barwari, T., Whitehead, M., Ramírez, C. M., Goedeke, L., et al. (2016) · Diabetes · doi:10.2337/db16-0731 · Cited by 257 · see citing works
“Moreover, our comprehensive assessment of plasma proteins returned a positive correlation with afamin, which was previously linked to prevalent and new-onset metabolic syndrome and all its components (34), a positive correlation with complement factor H, a protein that binds malondialdehyde epitopes and protects from…”
BackgroundComplement activation by heme as a secondary hit for atypical hemolytic uremic syndrome
Frimat, M., Tabarin, F., Dimitrov, J. D., Poitou, C., Halbwachs‐Mecarelli, L., Frémeaux‐Bacchi, V., & Roumenina, L. T. (2013) · Blood · doi:10.1182/blood-2013-03-489245 · Cited by 250 · see citing works
Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)
Leibundgut, G., Scipione, C. A., Yin, H., Schneider, M., Boffa, M. B., Green, S., Yang, X., Dennis, E. A., Witztum, J. L., Koschinsky, M. L., et al. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m040733 · Cited by 246 · see citing works
Ferrington, D. A., Sinha, D., & Kaarniranta, K. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.09.002 · Cited by 241 · see citing works
“It can potentiate drusen formation by inhibiting phagocytosis by macrophages and microglia to clear cellular debris present between RPE cells and Bruchs’membrane (Donoso et al., 2006, Buschini et al., 2011; Weismann et al., 2011).”
BackgroundThe Membrane Attack Complex in Aging Human Choriocapillaris
Mullins, R. F., Schoo, D. P., Sohn, E. H., Flamme‐Wiese, M. J., Workamelahu, G., Johnston, R. M., Wang, K., Tucker, B. A., & Stone, E. M. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.07.017 · Cited by 230 · see citing works
“In addition, the 402H form of CFH has a reduced affinity for Bruch’s membrane malondialdehyde.(46) Moreover, eyes homozygous for the Y402H polymorphism have increased deposition of MAC.”
BackgroundWhitmore, S. S., Sohn, E. H., Chirco, K. R., Drack, A. V., Stone, E. M., Tucker, B. A., & Mullins, R. F. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.11.005 · Cited by 219 · see citing works
“The Y402H allele reduces the ability of CFH to bind malondialdehyde adducts, potentially reducing the clearance of apoptotic cells (Weismann et al., 2011).”
BackgroundTsimikas, S., Willeit, P., Willeit, J., Santer, P., Mayr, M., Xu, Q., Mayr, A., Witztum, J. L., & Kiechl, S. J. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.08.979 · Cited by 219 · see citing works
“Recently, we demonstrated that complement factor H CFH), which is a primary regulator of the alternative athway of complement activation, strongly binds to MDA pitopes (24).”
Ceria‐Based Therapeutic Antioxidants for Biomedical Applications
Kim, Y. G., Lee, Y., Lee, N., Soh, M., Kim, D., & Hyeon, T. (2023) · Advanced Materials · doi:10.1002/adma.202210819 · Cited by 216 · see citing works
Protection of host cells by complement regulators
Schmidt, C. Q., Lambris, J. D., & Ricklin, D. (2016) · Immunological Reviews · doi:10.1111/imr.12475 · Cited by 211 · see citing works
Nrf2 signaling is impaired in the aging RPE given an oxidative insult
Sachdeva, M. M., Cano, M., & Handa, J. T. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2013.10.024 · Cited by 207 · see citing works
“To establish whether these levels of superoxide anion were associated with oxidative damage to the RPE, we performed immunolabeling for malondialdehyde (MDA), a known lipid peroxidation product that has been identified in AMD (Weismann et al., 2011).”
On phagocytes and macular degeneration
Guillonneau, X., Eandi, C. M., Paques, M., Sahel, J.-A., Sapieha, P., & Sennlaub, F. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.06.002 · Cited by 185 · see citing works
“…rather as an additional trait of CFH402H, adding to its previously described decreased capacity to (i) inhibit oxidative stress (Shaw et al., 2012; Weismann et al., 2011), and (ii) to bind to Bruchs membrane (Clark et al., 2010), which might protect the RPE against uncontrolled complement…”
BackgroundInfluentialComplement factor H in host defense and immune evasion
Parente, R., Clark, S. J., Inforzato, A., & Day, A. J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2418-4 · Cited by 193 · see citing works
“2), where the Y402H polymorphism leads to substantially impaired binding [123].”
BackgroundImmune mechanisms in inflammatory and degenerative eye disease
Perez, V. L., & Caspi, R. R. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.04.003 · Cited by 185 · see citing works
Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation
Calippe, B., Augustin, S., Beguier, F., Charles-Messance, H., Poupel, L., Conart, J.-B., Hu, S. J., Lavalette, S., Fauvet, A., Rayes, J., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.006 · Cited by 168 · see citing works
The innate immune response to products of phospholipid peroxidation
Weismann, D., & Binder, C. J. (2012) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2012.01.018 · Cited by 172 · see citing works
The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies
Domènech, E. B., & Marfany, G. (2020) · Antioxidants · doi:10.3390/antiox9040347 · Cited by 169 · see citing works
“The major genetic risk factor to develop AMD is the Y402H polymorphism of complement factor H (CFH), which reduces CFH’s ability to neutralize the effect of oxidized photoreceptor phospholipids from photoreceptors, which are incorporated into the RPE membrane and trigger RPE cell apoptosis [83,84].”
Backgroundvan Dijk, R. A., Kolodgie, F. D., Ravandi, A., Leibundgut, G., Hu, P., Prasad, A., Mahmud, E., Dennis, E. A., Curtiss, L. K., Witztum, J. L., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p030890 · Cited by 168 · see citing works
Abokyi, S., To, C. H., Lam, T. T., & Tse, D. Y. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/7901270 · Cited by 171 · see citing works
“In the Y402H polymorphism, there is a marked reduction in the ability of the complement regulator CFH to bind to MDA, a lipid peroxidation product [154], leading to uncontrolled MDA-induced inflammation.”
BackgroundInfluentialAgrón, E., Mares, J. A., Clemons, T. E., Swaroop, A., Chew, E. Y., & Keenan, T. D. L. (2020) · Ophthalmology · doi:10.1016/j.ophtha.2020.08.018 · Cited by 167 · see citing works
Zhu, L., Zhai, Y., Wang, F., Hou, P., Lv, J., Xu, D., Shi, S., Liu, L., Yu, F., Zhao, M., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014010096 · Cited by 166 · see citing works
Oxidative stress, innate immunity, and age-related macular degeneration
Shaw, P. X., Stiles, T. L., Douglas, C. R., Ho, D., Fan, W., Du, H., & Xu, X. (2016) · AIMS molecular science · doi:10.3934/molsci.2016.2.196 · Cited by 168 · see citing works
“Wild-type CFH demonstrates a substantially increased affinity for oxidatively modified lipids such as oxPLs and malondialdehyde (MDA) compared to native, un-oxidized lipids [8,115,116].”
BackgroundThe complotype: dictating risk for inflammation and infection
Harris, C. L., Heurich, M., de Córdoba, S. R., & Morgan, B. P. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.06.001 · Cited by 162 · see citing works
Complement factor H in AMD: Bridging genetic associations and pathobiology
Toomey, C. B., Johnson, L. V., & Rickman, C. B. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.09.001 · Cited by 160 · see citing works
“Using an unbiased proteomic approach to identify plasma proteins that interact with malondialdehyde (MDA), a marker of lipid peroxidation associated with oxidative stress, Weismann et al. discovered that CFH is a major MDA-binding protein and established it as an innate defense protein against MDA (Weismann et al., 20…”
BackgroundInfluentialHow does the macula protect itself from oxidative stress?
Handa, J. T. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.03.006 · Cited by 154 · see citing works
“Recently, in a multi-laboratory collaboration, we discovered that CFH, traditionally considered a major regulator of the alternative complement pathway, is a novel PRR that specifically recognizes MDA (Weismann et al., 2011).”
BackgroundImplications for reactive oxygen species in schizophrenia pathogenesis
Koga, M., Serritella, A. V., Sawa, A., & Sedlak, T. W. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.06.022 · Cited by 159 · see citing works
“Complement factor H appears to bind the lipid oxidation product, malonaldehyde, where it can attenuate further oxidative stress (Weismann et al., 2011).”
BackgroundOxidative stress and hepatitis C virus
Paracha, U. Z., Fatima, K., Alqahtani, M. H., Chaudhary, A., Abuzenadah, A. M., Damanhouri, G. A., & Qadri, I. (2013) · Virology Journal · doi:10.1186/1743-422x-10-251 · Cited by 156 · see citing works
Factor H: A Complement Regulator in Health and Disease, and a Mediator of Cellular Interactions
Kopp, A., Hebecker, M., Svobodová, E., & Józsi, M. (2012) · Biomolecules · doi:10.3390/biom2010046 · Cited by 157 · see citing works
“Malondialdehyde SCRs 7, 20 Protection from oxidative stress [50]”
BackgroundRegulation of age-related macular degeneration-like pathology by complement factor H
Toomey, C. B., Kelly, U., Saban, D. R., & Rickman, C. B. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424391112 · Cited by 156 · see citing works
“A recent study uncovered a function for CFH in blocking the damaging effects of the lipid peroxidation product, malondialdehyde (72).”
BackgroundLipid Peroxidation in Atherosclerotic Cardiovascular Diseases
Gianazza, E., Brioschi, M., Fernandez, A. M., Casalnuovo, F., Altomare, A., Aldini, G., & Banfi, C. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7955 · Cited by 158 · see citing works
“The MDA forms stable adducts with the major cellular biomolecules in different tissues and body fluids, such as lipids, proteins, free amino acids, and nucleotides, resulting in the loss of their structure and function and leading to alteration in cellular responses (281, 363, 401).”
Shaw, P. X., Zhang, L., Zhang, M., Du, H., Zhao, L., Lee, C., Grob, S., Lim, S. L., Hughes, G., Lee, J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121309109 · Cited by 148 · see citing works
“Recently, Weismann and coworkers (29) reported a link between CFH and oxidative stress in AMD.”
BackgroundClark, S. J., Ridge, L. A., Herbert, A. P., Hakobyan, S., Mulloy, B., Lennon, R., Würzner, R., Morgan, B. P., Uhrı́n, D., Bishop, P. N., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201751 · Cited by 148 · see citing works
“Another recent study has shown that a major CFH ligand is malondialdehyde (MDA), a common lipid peroxidation product found to accumulate in diseases such as AMD as a result of oxidative stress (46); for example, MDA is found on the surface of apoptotic/necrotic cells and blebs derived from these.”
InfluentialFactor H-related proteins determine complement-activating surfaces
Józsi, M., Tortajada, A., Uzonyi, B., de Jorge, E. G., & de Córdoba, S. R. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.04.008 · Cited by 144 · see citing works
Hajrasouliha, A. R., Jiang, G., Lu, Q., Lü, H., Kaplan, H. J., Zhang, H., & Shao, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.470765 · Cited by 145 · see citing works
Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration
Kersten, E., Paun, C. C., Schellevis, R. L., Hoyng, C. B., Delcourt, C., Lengyel, I., Pető, T., Ueffing, M., Klaver, C. C. W., Dammeier, S., et al. (2017) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2017.05.003 · Cited by 142 · see citing works
“Binding of MDA by IgM or macrophages leads to a proinflammatory response by increasing the expression of the inflammation factor interleukin (IL)-8,(274,358) whereas binding to FH attenuates inflammation.(358)”
BackgroundTisi, A., Feligioni, M., Passacantando, M., Ciancaglini, M., & Maccarone, R. (2021) · Cells · doi:10.3390/cells10010064 · Cited by 144 · see citing works
“ability to regulate the alternate complement pathway, the SCR7 domain is responsible for the CFH’s ability to bind lipid peroxidation products, such as malondialdehyde (MDA), released by the photoreceptors as a consequence of photo-oxidative stress [71].”
BackgroundContext-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation
Miller, Y. I., & Shyy, J. Y.-J. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.11.002 · Cited by 140 · see citing works
Oxidative Stress and Antioxidants in Age-Related Macular Degeneration
Kushwah, N. S., Bora, K., Maurya, M., Pavlovich, M. C., & Chen, J. (2023) · Antioxidants · doi:10.3390/antiox12071379 · Cited by 138 · see citing works
Regulation of regulators: Role of the complement factor H-related proteins
Cserhalmi, M., Papp, A., Brandus, B., Uzonyi, B., & Józsi, M. (2019) · Seminars in Immunology · doi:10.1016/j.smim.2019.101341 · Cited by 131 · see citing works
Sun, N., Chen, J., Wang, D., & Lin, S. (2018) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2018.08.010 · Cited by 132 · see citing works
Rational Engineering of a Minimized Immune Inhibitor with Unique Triple-Targeting Properties
Schmidt, C. Q., Bai, H., Lin, Z., Risitano, A. M., Barlow, P. N., Ricklin, D., & Lambris, J. D. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203548 · Cited by 131 · see citing works
“The involvement of complement in the pathology of prevalent diseases such as age-related macular degeneration (AMD), together with its upstream role in controlling inflammatory processes, has fueled efforts to design complementtargeted therapeutics (5, 6).”
BackgroundMethodInfluentialAge-related macular degeneration and the role of the complement system
McHarg, S., Clark, S. J., Day, A. J., & Bishop, P. N. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.02.032 · Cited by 126 · see citing works
Malondialdehyde epitopes as mediators of sterile inflammation
Busch, C. J., & Binder, C. J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.06.016 · Cited by 125 · see citing works
Clark, S. J., Schmidt, C. Q., White, A. M., Hakobyan, S., Morgan, B. P., & Bishop, P. N. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401613 · Cited by 122 · see citing works
“The unique FHL-1 C terminus means that it is necessary to investigate the binding characteristics of known FH ligands such as C-reactive protein (55, 56) and markers of oxidative stress (such as malondialdehyde) (57) in relationship to the Y402H polymorphism.”
BackgroundGenetic variants in the complement system predisposing to age-related macular degeneration: A review
Schramm, E. C., Clark, S. J., Triebwasser, M. P., Raychaudhuri, S., Seddon, J. M., & Atkinson, J. P. (2014) · Molecular Immunology · doi:10.1016/j.molimm.2014.06.032 · Cited by 121 · see citing works
“Furthermore, the Y402H polymorphism reduces the binding of FH to malondialdehyde (MDA), a peroxidation product that accumulates in AMD as a result of oxidative stress (Weismann et al., 2011).”
BackgroundInhibition of 12/15‐lipoxygenase as therapeutic strategy to treat stroke
Yiğitkanlı, K., Pekcec, A., Karataş, H., Pallast, S., Mandeville, E. T., Joshi, N., Smirnova, N., Gazaryan, I. G., Ratan, R. R., Witztum, J. L., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23734 · Cited by 121 · see citing works
PyTMs: a useful PyMOL plugin for modeling common post-translational modifications
Warnecke, A., Sandalova, T., Achour, A., & Harris, R. A. (2014) · BMC Bioinformatics · doi:10.1186/s12859-014-0370-6 · Cited by 120 · see citing works
“There are accumulating examples of specific PTMs being recognized by scavenger receptors, complement components and antibodies due to alterations in structure and charge [12,15-17].”
Tsiantoulas, D., Perkmann, T., Afonyushkin, T., Mangold, A., Prohaska, T. A., Papac-Miličević, N., Millischer, V., Bartel, C., Hörkkö, S., Boulanger, C. M., et al. (2014) · Journal of Lipid Research · doi:10.1194/jlr.p054569 · Cited by 118 · see citing works
“(16, 34) To test whether MP induce chemokine expression via MDA-epitopes, we determined IL-8 secretion by THP-1 cells or primary human monocytes that were stimulated with platelet-derived MP in the presence of the MDA/MAA-specific IgM LR04 or an isotype control.”
Cruz‐Guilloty, F., Saeed, A. M., Echegaray, J. J., Duffort, S., Ballmick, A., Tan, Y., Betancourt, M., Viteri, E. J., Ramkhellawan, G. C., Ewald, E. J., et al. (2013) · International Journal of Inflammation · doi:10.1155/2013/503725 · Cited by 118 · see citing works
“For instance, it was recently demonstrated that complement factor H (CFH) serves a protective role in AMD by binding and inhibiting the inflammatory effects of the lipid peroxidation product malondialdehyde (MDA) [16] .”
BackgroundFunctional Anatomy of Complement Factor H
Makou, E., Herbert, A. P., & Barlow, P. N. (2013) · Biochemistry · doi:10.1021/bi4003452 · Cited by 115 · see citing works
Jun, S., Datta, S., Wang, L., Pegany, R. B., Cano, M., & Handa, J. T. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.09.023 · Cited by 115 · see citing works
Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related macular degeneration.
Handa, J. T., Cano, M., Wang, L., Datta, S., & Liu, T. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.07.013 · Cited by 112 · see citing works
Choroidal Neovascularization: Mechanisms of Endothelial Dysfunction
Yeo, N. J. Y., Chan, E. J. J., & Cheung, C. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01363 · Cited by 117 · see citing works
Chen, J., Zeng, L., Xia, T., Li, S., Yan, T., Wu, S., Qiu, G., & Liu, Z. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02032 · Cited by 112 · see citing works
Complement dysregulation and disease: From genes and proteins to diagnostics and drugs
de Córdoba, S. R., Tortajada, A., Harris, C. L., & Morgan, B. P. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.07.021 · Cited by 109 · see citing works
Moss‐made pharmaceuticals: from bench to bedside
Ralf Reski, A., Parsons, J., & Decker, E. L. (2015) · Plant Biotechnology Journal · doi:10.1111/pbi.12401 · Cited by 110 · see citing works
Malondialdehyde Epitopes as Targets of Immunity and the Implications for Atherosclerosis
Papac-Miličević, N., Busch, C. J., & Binder, C. J. (2016) · Advances in immunology · doi:10.1016/bs.ai.2016.02.001 · Cited by 109 · see citing works
“…of MDA epitopes identified so far are apoptotic/necrotic cells (Amir et al., 2012; Chang et al., 1999; Chang et al., 2004; Chou et al., 2009; Weismann et al., 2011), microvesicles (MV) (Huber et al., 2002; Liu, Scalia, Mehta, & Williams, 2012; Tsiantoulas et al., 2015) and oxidized…”
BackgroundMethodInfluentialYu, Y., Triebwasser, M. P., Wong, E. K. S., Schramm, E. C., Thomas, B., Reynolds, R. C., Mardis, E. R., Atkinson, J. P., Daly, M. J., Raychaudhuri, S., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu226 · Cited by 108 · see citing works
Gorin, M. B. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.04.004 · Cited by 105 · see citing works
“For example, Weissman et al (Weismann et al., 2011) has reported that the Y402H variant specifically affects the ability of complement factor H protein to bind malondialdehyde a common lipid peroxidation product that has been implicated in AMD.”
BackgroundLandowski, M., Kelly, U., Klingeborn, M., Groelle, M., Ding, J., Grigsby, D., & Rickman, C. B. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814014116 · Cited by 103 · see citing works
“The Y402H polymorphism has been shown to decrease the binding of CFH to heparin (21, 25), M6 protein of Streptococcus pyogenes (25, 26), CRP (21, 25–27), Bruch’s membrane (BrM) (28), malondialdehyde (MDA) epitopes (29), and oxidized phospholipids (30).”
BackgroundKanner, J., Gorelik, S., Sirota, R., & Kohen, R. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf300193g · Cited by 103 · see citing works
Cipriani, V., Lorés‐Motta, L., He, F., Fathalla, D., Tilakaratna, V., McHarg, S., Bayatti, N., Acar, İ. E., Hoyng, C. B., Fauser, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14499-3 · Cited by 102 · see citing works
Cano, M., Wang, L., Wan, J., Barnett, B. P., Ebrahimi, K. B., Qian, J. X., & Handa, J. T. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.01.004 · Cited by 102 · see citing works
Piccardi, M., Marangoni, D., Minnella, A. M., Savastano, M. C., Valentini, P., Ambrosio, L., Capoluongo, E., Maccarone, R., Bisti, S., & Falsini, B. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/429124 · Cited by 102 · see citing works
The Proteomics of DrusenPreprint
Crabb, J. W. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a017194 · Cited by 103 · see citing works
“Multiple lipoxidation products are present in drusen, Bruch’s membrane, and the cellular debris that copurifies with RPE lipofuscin granules (Crabb et al. 2002a; Gu et al. 2003a; Schutt et al. 2003; Shen et al. 2007; Ng et al. 2008; Weismann et al. 2011; Shaw et al. 2012).”
BackgroundInfluentialMicklisch, S., Lin, Y., Jacob, S., Karlstetter, M., Dannhausen, K., Dasari, P., von der Heide, M., Dahse, H., Schmölz, L., Graßmann, F., et al. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0776-3 · Cited by 101 · see citing works
“Notably, in addition to surface complement activation, complement regulators like factor H and C4bp are recruited to the surfaces to restrict the complement cascade and to inhibit inflammation and autoimmune reactions [3, 21, 22].”
BackgroundNita, M., Grzybowski, A. E., Ascaso, F. J., & Huerva, V. (2014) · Mediators of Inflammation · doi:10.1155/2014/930671 · Cited by 123 · see citing works
“CFH binds to antigen epitopes, the part of an antigen recognized by antibodies, B cells, or T cells, and protects against oxidative stress [75].”
BackgroundSaccà, S. C., Roszkowska, A. M., & Izzotti, A. (2013) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2013.01.001 · Cited by 99 · see citing works
“These feature includes mutations in genes encoding for: (a) complement system factor 3 [302], and 5 [303]; the important role of complement factor H in protecting from oxidative stress and specifically from malondialdehyde products as occurring in AMD lesions have been demonstrated [304]; (b) HTRA1 secreted serine pro…”
BackgroundOxidation-Specific Biomarkers and Risk of Peripheral Artery Disease
Bertoia, M. L., Pai, J. K., Lee, J. H., Taleb, A., Joosten, M. M., Mittleman, M. A., Yang, X., Witztum, J. L., Rimm, E. B., Tsimikas, S., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.02.047 · Cited by 97 · see citing works
“In response to uch danger-associated molecular patterns, macrophage cavenger receptors, immune effector proteins such as autontibodies to malondialdehyde-modified low-density liporotein (MDA-LDL), complement factor H (12), and -reactive protein have been selected and expanded to bind nd neutralize their pro-inflammato…”
Kenney, M. C., Chwa, M., Atilano, S. R., Pavlis, J. M., Falatoonzadeh, P., Ramírez, C., Malik, D., Hsu, T., Woo, G., Soe, K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054339 · Cited by 96 · see citing works
“The CFH protein with the high risk Tyr402His polymorphism has a reduced capacity to bind with malondialdehyde (MDA), a lipid peroxidation cytotoxin, which could possibly contribute to a defective innate immune response for AMD patients [47].”
BackgroundMalaria Parasites Co-opt Human Factor H to Prevent Complement-Mediated Lysis in the Mosquito Midgut
Simon, N., Lasonder, E., Scheuermayer, M., Kuehn, A., Tews, S., Fischer, R., Zipfel, P. F., Skerka, C., & Pradel, G. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2012.11.013 · Cited by 94 · see citing works
“For the latter two C3b-binding sites and for module CCP7 heparin binding was described (Kühn et al., 1995; Blackmore et al., 1998; Prodinger et al., 1998; Weismann et al., 2011).”
Background
- Authors
- Weismann, D., Hartvigsen, K., Lauer, N., Bennett, K. L., Scholl, H. P. N., Issa, P. C., Cano, M., Brandstätter, H., Tsimikas, S., Skerka, C., Superti-Furga, G., Handa, J. T., Zipfel, P. F., Witztum, J. L., & Binder, C. J.
- Affiliations
- Austrian Academy of Sciences (AT)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Johns Hopkins University (US)
- University of Oxford (GB)
- Octapharma (Austria) (AT)
- University of California San Diego (US)
- Corresponding author
- Binder, Christoph J.
- ORCID
- Venue
- Nature
- Published
- 2011-10
- Volume
- 478
- Issue
- 7367
- Pages
- 76-81
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4826616
- OpenAlex
- W2062097745
- Cited by
- 533
- References
- 42
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 25 · 2023: 30 · 2022: 29 · 2021: 42 · 2020: 36 · 2019: 29 · 2018: 33 · 2017: 31 · 2016: 39 · 2015: 42 · 2014: 44 · 2013: 66 · 2012: 44
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01-HL086599, HL-088093, P01HL088093)
- National Eye Institute (EY14005, R01EY014005, EY019044, R01EY019904)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- complement factor H, malondialdehyde, lipid peroxidation, oxidative stress, age-related macular degeneration, macrophage uptake, pro-inflammatory effects, innate immunity, chronic inflammation, retina
- MeSH terms
- Animals, Epitopes, Binding Sites, Complement System Proteins, Complement Inactivator Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Inflammation, Macular Degeneration, Male, Malondialdehyde, Mice, Inbred C57BL, Mutation, Necrosis, Protein Binding, Retina, Lipid Peroxidation, Apoptosis, Complement Factor H, Protein Structure, Tertiary, Macrophages, Peritoneal, Oxidative Stress, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
