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Monocytes and Neutrophils Oxidize Low Density Lipoprotein Making It Cytotoxic
Abstract
Free radicals are believed to be involved in leukocyte induced tissue injury. The present studies were performed to determine whether low density lipoprotein (LDL) might serve as a mediator of tissue injury after leukocyte induced free radical oxidation of LDL. Our results show that incubation of LDL with monocytes or polymorphonuclear leukocytes (PMN) leads to oxidation of the lipoprotein rendering it toxic to proliferating fibroblasts. Monocyte activation enhances these effects. Butylated hydroxytoluene (BHT), vitamin E (vit E) and glutathione (GSH) virtually prevent the oxidation of LDL and the formation of cytotoxic LDL, indicating that these alterations are mediated by leukocyte-derived free radicals. This is the first demonstration that short-lived free radicals emanating from phagocytic cells could mediate cell injury through the action of a stable cytotoxin formed by the oxidation of LDL. The fact that lipoproteins can transfer a cytotoxic effect from leukocytes to proliferating cells reveals a pathway for cell destruction which may have implications in atherosclerotic plaque progression, macrophage mediated toxicity to tumor cells and tissue injury by inflammatory processes.
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Cited by
Middleton, E., Kandaswami, C., & Theoharides, T. C. (2000) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01472-8 · Cited by 4,882
Daugherty, A., Dunn, J. L., Rateri, D. L., & Heinecke, J. W. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117342 · Cited by 1,269
Phagocytes and oxidative stress
Babior, B. M. (2000) · The American Journal of Medicine · doi:10.1016/s0002-9343(00)00481-2 · Cited by 1,061
Vascular endothelium – Gatekeeper of vessel health
Cahill, P. A., & Redmond, E. M. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.03.007 · Cited by 518
Retsky, K. L., Freeman, M. W., & Frei, B. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54075-8 · Cited by 271
Hazell, L. J., van den Berg, J. J. M., & Stocker, R. (1994) · Biochemical Journal · doi:10.1042/bj3020297 · Cited by 267
Vendrov, A. E., Hakim, Z. S., Madamanchi, N. R., Rojas, M., Madamanchi, C., & Runge, M. S. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.152629 · Cited by 173
Kirk, E. A., Dinauer, M. C., Rosen, H., Chait, A., Heinecke, J. W., & LeBoeuf, R. C. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.6.1529 · Cited by 171
Spickett, C. M., Jerlich, A., Panasenko, O. M., Arnhold, J., Pitt, A. R., Stelmaszyńska, T., & Schaur, R. J. (2000) · Acta Biochimica Polonica · doi:10.18388/abp.2000_3944 · Cited by 154
Vitamin E Inhibits Lysophosphatidylcholine-Induced Endothelial Dysfunction and Platelet Activation
Murohara, T., Ikeda, H., Katoh, A., Takajo, Y., Otsuka, Y., Haramaki, N., & Imaizumi, T. (2002) · Antioxidants & Redox Signaling · doi:10.1089/152308602760598945 · Cited by 19
Metadata
- Authors
- Cathcart, M. K., Morel, D. W., & Chisolm, G. M.
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 1985-08-01
- Volume
- 38
- Issue
- 2
- Pages
- 341-350
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W1871621847
- Cited by
- 526
- References
- 0
- FWCI
- 5.59
- Type
- journal article
- Language
- en
- Open access
- closed
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