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-α (TNF-α); the mechanisms involved are unresolved. The microtubule stabilizer taxol shared two actions of LPS on macrophages: it rapidly decreased TNF-α receptors and triggered TNF-α 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-α by both stimuli but did not block the decrease in TNF-α receptors. Thus, a protein associated with microtubules may be a cellular target of LPS.