Shared actions of endotoxin and taxol on TNF receptors and TNF release.
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.
Ding
A H
AH
Department of Medicine, Cornell University Medical College, New York, NY 10021.
Porteu
F
F
Sanchez
E
E
Nathan
C F
CF
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D003433:Crosses, Genetic; D003907:Dexamethasone / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017239:Paclitaxel; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000470:Alkaloids; D008070:Lipopolysaccharides; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D017239:Paclitaxel