A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides.
Open accessAbstract
In this study we have used homogenates of human atheromatous plaque as immunogen to establish a murine monoclonal antibody which recognizes oxidized low density lipoprotein (LDL). This monoclonal antibody, FOH1a/DLH3, reacted with oxidized LDL, but enzyme-linked immunosorbent assay showed that it had no reaction with native, acetylated, or malonaldehyde-treated LDL. The antibody cross-reacted with oxidized high density lipoprotein, suggesting that specific sequences of the apolipoprotein B are not essential for antigen recognition by the antibody. Immunohistochemical analysis of thin paraffin sections from human coronary arteries showed that foam cells derived from macrophages in atherosclerotic lesions were heavily stained by this antibody. Several other structures in the lesions, including swollen collagen fibers, cellular debris in necrotic cores, and endothelial cells, were moderately stained. The epitope of this antibody was characterized by a model antigen-generating system using ferrous ion-induced peroxidation of lipids. When the total lipid fraction extracted from LDL was treated with the ferrous ion-induced peroxidation system, the reaction mixture was recognized by the antibody. Antigenic product(s) was produced only when phosphatidylcholine (PC) was treated with the ferrous ion-induced peroxidation, other lipids failed to react to the antibody. To investigate the possible formation of a complex of antigenic product with a polypeptide, a synthetic peptide and a rabbit antiserum against the peptide were used. Reaction mixture of ferrous ion-induced peroxidation of PC in the presence of the peptide was added to a microtiter well precoated with the monoclonal antibody FOH1a/DLH3. After washing, the peptide remaining in the well was detected with rabbit antiserum against the peptide, whereas no reactivity was observed when peptide alone was added to the well. Binding of the antigenic complex to the precoated monoclonal antibody was competed by oxidized PC produced in the absence of any polypeptide. We conclude that oxidized phospholipid product(s) is the epitope of the monoclonal antibody and that the oxidized phospholipid forms complexes with polypeptides. The antigenic materials are detected in foam cells in atherosclerotic lesions.
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?
LDL oxidation is an important aspect of the pathogenic mechanism of atherosclerosis.
“From the viewpoint of cell biology672, 673), immunohistology674, 675) and other factors, it has become clear that LDL oxidation is an important aspect of the pathogenic mechanism of atherosclerosis.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [672]
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
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/o59-099 · Cited by 54,751 · see citing works
A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
Bligh, E. G., & Dyer, W. J. (1959) · Canadian Journal of Biochemistry and Physiology · doi:10.1139/y59-099 · Cited by 23,189 · see citing works
Measurement of protein using bicinchoninic acid
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., & Klenk, D. C. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90442-7 · Cited by 18,482 · see citing works
[30] Microsomal lipid peroxidation
Buege, J. A., & Aust, S. D. (1978) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(78)52032-6 · Cited by 13,437 · see citing works
Role of oxidized low density lipoprotein in atherogenesis.
Witztum, J. L., & Steinberg, D. H. (1991) · Journal of Clinical Investigation · doi:10.1172/jci115499 · Cited by 2,682 · see citing works
Goldstein, J. L., Ho, Y. K., Basu, S. K., & Brown, M. S. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.1.333 · Cited by 2,447 · see citing works
LIPOPROTEIN METABOLISM IN THE MACROPHAGE: Implications for Cholesterol Deposition in Atherosclerosis
Brown, M. S., & Goldstein, J. L. (1983) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.52.070183.001255 · Cited by 2,300 · see citing works
Ylä‐Herttuala, S., Palinski, W., Rosenfeld, M. E., Parthasarathy, S., Carew, T. E., Butler, S. S., Witztum, J. L., & Steinberg, D. H. (1989) · Journal of Clinical Investigation · doi:10.1172/jci114271 · Cited by 1,877 · see citing works
Steinbrecher, U. P., Parthasarathy, S., Leake, D. S., Witztum, J. L., & Steinberg, D. I. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.12.3883 · Cited by 1,626 · see citing works
CD36 is a receptor for oxidized low density lipoprotein
Endemann, G., Stanton, L. W., Madden, K. S., Bryant, C. M., White, R. T., & Protter, A. A. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50272-1 · Cited by 1,282 · see citing works
Separation of plasma lipoproteins by density-gradient ultracentrifugation
Redgrave, T. G., Roberts, D., & West, C. E. (1975) · Analytical Biochemistry · doi:10.1016/0003-2697(75)90488-1 · Cited by 1,101 · see citing works
Type I macrophage scavenger receptor contains α-helical and collagen-like coiled coils
Kodama, T., Freeman, M. W., Rohrer, L., Zabrecky, J. R., Matsudaira, P. T., & Krieger, M. (1990) · Nature · doi:10.1038/343531a0 · Cited by 1,039 · see citing works
Basu, S. K., Goldstein, J. L., Anderson, G. W., & Brown, M. S. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.9.3178 · Cited by 1,021 · see citing works
Fogelman, A. M., Shechter, I., Seager, J., Hokom, M. M., CHILD, J. S., & Edwards, P. A. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.4.2214 · Cited by 849 · see citing works
Malondialdehyde-Altered Protein Occurs in Atheroma of Watanabe Heritable Hyperlipidemic Rabbits
Haberland, M. E., Fong, D., & Cheng, L. (1988) · Science · doi:10.1126/science.2455346 · Cited by 748 · see citing works
Palinski, W., Ylä‐Herttuala, S., Rosenfeld, M. E., Butler, S. W., Socher, S. S., Parthasarathy, S., Curtiss, L. K., & Witztum, J. L. (1990) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.10.3.325 · Cited by 616 · see citing works
Rosenfeld, M. E., Palinski, W., Ylä‐Herttuala, S., Butler, S. S., & Witztum, J. L. (1990) · Arteriosclerosis An Official Journal of the American Heart Association Inc · doi:10.1161/01.atv.10.3.336 · Cited by 474 · see citing works
Matsumoto, A., Naito, M., Itakura, H., Ikemoto, S., Asaoka, H., Hayakawa, I., Kanamori, H., Aburatani, H., Takaku, F., & Suzuki, H. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.23.9133 · Cited by 358 · see citing works
O’Brien, P. J. (1969) · Canadian Journal of Biochemistry · doi:10.1139/o69-076 · Cited by 351 · see citing works
Mahley, R. W., Innerarity, T. L., Weisgraber, K. H., & Oh, S. Y. (1979) · Journal of Clinical Investigation · doi:10.1172/jci109518 · Cited by 316 · see citing works
Graham, A., Hogg, N., Kalyanaraman, B., O'leary, V. J., Darley-Usmar, V. M., & Moncada, S. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)80269-z · Cited by 278 · see citing works
Purification and characterization of a bovine acetyl low density lipoprotein receptor.
Kodama, T., Reddy, P., Kishimoto, C., & Krieger, M. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.23.9238 · Cited by 259 · see citing works
Boyd, H. C., Gown, A. M., Wolfbauer, G., & Chait, A. (1989) · PubMed Central · Cited by 244 · see citing works
Role of fluids in transport and fractionation of uranium and thorium in magmatic processes
Keppler, H., & Wyllie, P. J. (1990) · Nature · doi:10.1038/348531a0 · Cited by 232 · see citing works
Stremler, K. E., Stafforini, D. M., Prescott, S. M., Zimmerman, G. A., & McIntyre, T. M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)83548-7 · Cited by 227 · see citing works
Steinbrecher, U. P., & Pritchard, P. H. (1989) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38359-0 · Cited by 215 · see citing works
A macrophage Fc receptor for IgG is also a receptor for oxidized low density lipoprotein.
Stanton, L. W., White, R. T., Bryant, C. M., Protter, A. A., & Endemann, G. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41692-4 · Cited by 192 · see citing works
Improved procedures for the determination of lipid phosphorus by malachite green.
Zhou, X., & Arthur, G. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)40776-x · Cited by 157 · see citing works
Oxidized low density lipoprotein is resistant to cathepsins and accumulates within macrophages
Lougheed, M., Zhang, H. F., & Steinbrecher, U. P. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98717-x · Cited by 147 · see citing works
Lipids and oxidised lipids in human atheroma and normal aorta
Carpenter, K. L. H., Taylor, S. E., Ballantine, J. A., et al. (1993) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(93)90151-x · Cited by 145 · see citing works
Mangin, E., Kugiyama, K., Nguy, J. H., Kerns, S. A., & Henry, P. D. (1993) · Circulation Research · doi:10.1161/01.res.72.1.161 · Cited by 144 · see citing works
Oxidation of lipoprotein Lp(a). A comparison with low-density lipoproteins
Sattler, W., Kostner, G. M., Waeg, G., et al. (1991) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(91)90251-c · Cited by 137 · see citing works
Hoff, H. F., Whitaker, T. E., & O'Neil, J. C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48537-7 · Cited by 136 · see citing works
The intracellular storage and turnover of apolipoprotein B of oxidized LDL in macrophages
Jessup, W., Mander, E. L., & Dean, R. T. (1992) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(92)90287-6 · Cited by 122 · see citing works
Vijayagopal, P., Srinivasan, S. R., Jones, K. M., Radhakrishnamurthy, B., & Berenson, G. S. (1985) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(85)90048-7 · Cited by 92 · see citing works
Bhadra, S., Arshad, M. A. Q., Rymaszewski, Z., et al. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)90942-z · Cited by 76 · see citing works
Identification of cholesterol‐bound aldehydes in copper‐oxidized low density lipoprotein
KAMIDO, H., Kuksis, A., Marai, L., et al. (1992) · FEBS Letters · doi:10.1016/0014-5793(92)80635-t · Cited by 59 · see citing works
Tanaka, T., Minamino, H., Unezaki, S., et al. (1993) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(93)90107-k · Cited by 59 · see citing works
Defective catabolism of oxidized LDL by J774 murine macrophages.
Roma, P., Bernini, F., Fogliatto, R., Bertulli, S. M., Negri, S., Fumagalli, R., & Catapano, A. L. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41507-x · Cited by 59 · see citing works
Wang, T., & Powell, W. S. (1991) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(91)90211-y · Cited by 54 · see citing works
Wang, T., Yu, W., & Powell, W. S. (1992) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)41618-9 · Cited by 49 · see citing works
Itabe, H., Kushi, Y., Handa, S., & Keizo, I. (1988) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(88)90089-6 · Cited by 45 · see citing works
Self-citationMonoclonal DLR1a/104G antibody recognizing peroxidized lipoproteins in atherosclerotic lesions
MOWRI, H.-O., Ohkuma, S., & Takano, T. (1988) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(88)90282-2 · Cited by 39 · see citing works
Self-citationImmunogenicity of malondialdehyde-modified low density lipoproteins
Gonen, B., Fallon, J. J., & Baker, S. A. (1987) · Atherosclerosis · doi:10.1016/0021-9150(87)90042-6 · Cited by 30 · see citing works
Novel phospholipids with aliphatic dicarboxylic acid residues in a lipid extract from bovine brain
Tokumura, A., Asai, T., Takauchi, K., Kamiyasu, K., Ogawa, T., & Tsukatani, H. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80575-8 · Cited by 27 · see citing works
Kimura, J., Nakagami, K., Amanuma, K., Ohkuma, S., Yoshida, Y., & Takano, T. (1987) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/bf00713521 · Cited by 21 · see citing works
Self-citationGalis, Z. S., Ghitescu, L. D., Li, Z., ALAVI, M. Z., & Moore, S. (1992) · PubMed · Cited by 13 · see citing works
Flagged first, then by citations
Research works printed but not linked: 3
- berg, D. (1984) Proc. Natl. h a d . Sci. U. S. A. 81,3883-3887
- Goldstein, J. L., Ho, Y. K., Basu, S . K., and Brown, M. S . (1979) Proc. Natl.
- Kodama, T., Reddy, P., Kishimoto, C., and Krieger, M. (1988) Proc. Natl. Acad. Acad. Sci. U. S. A. 76, 333-337
Cited by
Sorted by citations
Kinoshita, M., Yokote, K., Arai, H., Iida, M., Ishigaki, Y., Ishibashi, S., Umemoto, S., Egusa, G., Ohmura, H., Okamura, T., et al. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.gl2017 · Cited by 813 · see citing works
Öörni, K., Pentikäinen, M. O., Ala-Korpela, M., & Kovanen, P. T. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31964-7 · Cited by 252 · see citing works
Oxidized Phosphatidylcholines That Modify Proteins
Itabe, H., Yamamoto, H., Suzuki, M., Kawai, Y., Nakagawa, Y., Suzuki, A., Imanaka, T., & Takano, T. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.52.33208 · Cited by 128 · see citing works
Self-citationOkura, Y., Brink, M., Itabe, H., Scheidegger, K. J., Kalangos, A., & Delafontaine, P. (2000) · Circulation · doi:10.1161/01.cir.102.22.2680 · Cited by 126 · see citing works
Self-citationItabe, H. (2012) · Journal of Clinical Biochemistry and Nutrition · doi:10.3164/jcbn.11-00020r1 · Cited by 87 · see citing works
- Authors
- Itabe, H., Takeshima, E., Iwasaki, H., Kimura, J., Yoshida, Y., Imanaka, T., & Takano, T.
- Affiliations
- Teikyo University (JP)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-05
- Volume
- 269
- Issue
- 21
- Pages
- 15274-15279
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1487930529
- Cited by
- 282
- References
- 47
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 6 · 2017: 6 · 2016: 5 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 8
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Tokyo Medical and Dental University
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
- Keywords
- oxidized LDL, monoclonal antibodies, foam cells, atherosclerosis, oxidized phosphatidylcholine, macrophages, oxidized high-density lipoprotein, apolipoprotein B
- MeSH terms
- Amino Acid Sequence, Antibodies, Monoclonal, Antigen-Antibody Reactions, Arteriosclerosis, Cross Reactions, Foam Cells, Humans, Immunohistochemistry, Lipoproteins, LDL, Molecular Sequence Data, Oxidation-Reduction, Peptides, Phosphatidylcholines
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
