Abstract
LIPID A is the active moiety of lipopolysaccharide (LPS, also referred to as endotoxin), a surface component of Gram-negative bacteria that stimulates macrophage activation and causes endotoxic shock1, 2. Macrophages can bind, internalize and partially degrade LPS, lipid A and its bioactive precursor, lipid IVA (refs 3–7). We report here that lipid IVA binding and subsequent metabolism to a less active form by macrophage-like RAW 264.7 cells is mediated by the macrophage scavenger receptor. Scavenger-receptor ligands inhibit lipid IVA binding to, and metabolism by, RAW cells, and lipid IVA binds to type I and type II bovine scavenger receptors on transfected Chinese hamster ovary cells. Although in vitro competition studies with RAW cells indicate that scavenger receptor binding is not involved in LPS or lipid IVA-induced stimulation of macrophages, in vivo studies show that scavenger-receptor ligands greatly inhibit hepatic uptake of lipid IVA in mice. Thus, scavenger receptors expressed on macrophages may have an important role in the clearance and detoxification of endotoxin in animals.
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References
Raetz, C. R. H. A. Rev. Biochem. 59, 129–170 (1990).
Morrison, D. C. & Ryan, J. L. A. Rev. Med. 38, 417–432 (1987).
Peterson, A. A. & Munford, R. S. Infect. Immunity 55, 974–978 (1987).
Duncan, R. L. & Morrison, D. C. J. Immun. 132, 1416–1424 (1984).
Raetz, C. R. H. et al. Cold Spring Harb. Symp. quant Biol. 53, 973–982 (1988).
Hampton, R. Y., Golenbock, D. T. & Raetz, C. R. H. J. biol. Chem. 263, 14802–14807 (1988).
Golenbock, D. T., Hampton, R. Y., Raetz, C. R. H. & Wright, S. D. Infect. Immunity 58, 4069–4075 (1990).
Brown, M. S. & Goldstein, J. L. A. Rev. Biochem. 52, 223–261 (1983).
Hara, H., Tanashita, H., Yokoyama, S., Tajima, S. & Yamamamoto, A. Biochem. biophys. Res. Commun. 146, 802–808 (1987).
Kodama, T., Reddy, P., Kishimoto, C. & Krieger, M. Proc. natn. Acad. Sci. U.S.A. 85, 9238–9242 (1988).
Loppnow, H. et al. J. Immun. 142, 3229–3238 (1989).
Kodama, T. et al. Nature 343, 531–535 (1990).
Rohrer, L., Freeman, M., Kodama, T., Penman, M. & Krieger, M. Nature 343, 570–572 (1990).
Freeman, M. et al. Proc. natn. Acad. Sci. U.S.A. 88, 4931–4935 (1991).
Krieger, M. Cell 33, 413–422 (1983).
Goldstein, J. L., Ho, Y. K., Basu, S. K. & Brown, M. S. Proc. natn. Acad. Sci. U.S.A. 76, 333–337 (1979).
Hamilton, T. A., Ma, G. & Chisolm, G. M. J. Immun. 144, 2343–2350 (1990).
Pitas, R. E. J. biol. Chem. 265, 12722–12727 (1990).
Nishikama, K., Arai, H. & Inoue, K. J. biol. Chem. 265, 5226–5231 (1990).
Beutler, B. & Cerami, A. Biochemistry 27, 7575–7582 (1988).
Sheehan, K. C. F., Ruddle, N. H. & Schreiber, R. D. J. Immun. 142, 3884–3893 (1989).
Freudenberg, M. A., Kleine, B. & Galanos, C. Rev. Infec. Dis. 6, 483–487 (1984).
Nagelkerke, J. F., Barto, K. P. & Van Berkel, T. J. J. biol. Chem. 258, 12221–12227 (1983).
Pitas, R. E., Bayles, J., Mahley, R. W. & Bissel, D. M. J. Cell Biol. 100, 103–117 (1985).
Dresel, H. A. et al. EMBO J. 6, 319–326 (1987).
Van Berkel, T. J. C., De Rijke, Y. B. & Kruit, J. K. J. biol. Chem. 266, 2282–2289 (1991).
Kaplan, H. M., Brewer, N. R. & Blair, W. H. in The Mouse in Blomedical Research, Vol. 3 Normative Biology, Immunology and Husbandry (eds Foster, H. L., Small, D. J. & Fox, J. G.) 248–278 (Academic, New York, 1983).
Tobias, P. T., Soldau, K. & Ulevitch, R. J. J. biol. Chem. 264, 10867–10871 (1989).
chumann, R. R. et al. Science 249, 1429–1431 (1990).
Wright, S. D., Ramos, R. A., Tobias, P. S., Ulevitch, R. J. & Matheson, J. C. Science 249, 1431–1433 (1990).
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Hampton, R., Golenbock, D., Penman, M. et al. Recognition and plasma clearance of endotoxin by scavenger receptors. Nature 352, 342–344 (1991). https://doi.org/10.1038/352342a0
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DOI: https://doi.org/10.1038/352342a0
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