Endotoxin-refractory liver macrophages secrete tumor necrosis factor-alpha upon viral infection.
Rat liver macrophages (Kupffer cells) secrete tumor necrosis factor-alpha (cachectin) after exposure to Newcastle disease virus or bacterial endotoxin. Macrophages treated with endotoxin become refractory and fail to release tumor necrosis factor-alpha to a secondary challenge with endotoxin. The acquisition of the refractory state is dose-dependent, requires the continuous presence of endotoxin for a minimum of 8 h, is transient, and reversible. Endotoxin, however, renders Kupffer cells unresponsive only to itself. When endotoxin-refractory macrophages are activated by Newcastle disease virus, they still secrete tumor necrosis factor-alpha in amounts expected with this stimulus. Immunoprecipitation studies show that the precursor of tumor necrosis factor-alpha is found only in lysates of endotoxin-sensitive, but not in refractory macrophages, thus arguing against a post-translational regulatory process. Whereas prostaglandin E2 inhibits the production of tumor necrosis factor-alpha in response to endotoxin and viruses, it does not appear to mediate the refractory state.
Busam
K J
KJ
Biochemisches Institut, Albert-Ludwigs-Universität, Freiburg, Germany.
Schulze-Specking
A
A
Decker
K
K
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009521:Newcastle Disease / Q000378:metabolism*; D011233:Precipitin Tests; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone