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Science 20 April 1990:
Vol. 248. no. 4953, pp. 370 - 372
DOI: 10.1126/science.1970196
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Articles

Science, Vol 248, Issue 4953, 370-372
Copyright © 1990 by American Association for the Advancement of Science

articles

Shared actions of endotoxin and taxol on TNF receptors and TNF release

AH Ding, F Porteu, E Sanchez, and CF Nathan

Department of Medicine, Cornell University Medical College, New York, NY 10021.

Bacterial lipopolysaccharide (LPS) exerts profound effects on mammalian hosts in part by inducing macrophages to release tumor necrosis factor-alpha (TNF-alpha); the mechanisms involved are unresolved. The microtubule stabilizer taxol shared two actions of LPS on macrophages: it rapidly decreased TNF-alpha receptors and triggered TNF-alpha release. Both actions of taxol were absent in LPS-hyporesponsive C3H/HeJ mice. In recombinant inbred mice, the genes controlling responses to LPS and to taxol were closely linked. Dexamethasone blocked release of TNF-alpha by both stimuli but did not block the decrease in TNF-alpha receptors. Thus, a protein associated with microtubules may be a cellular target of LPS.


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