Recombinant tumour necrosis factor (TNF) fixed to cell monolayers retains its cytotoxic and growth-stimulatory activity. Evidence that internalization of TNF is not necessary for induction of biological effects.
Recombinant human tumour necrosis factor (rTNF) retained its cytotoxic activity after being fixed with paraformaldehyde to adherent cell monolayers. The cytotoxicity appeared to be mainly due to fixed rTNF and not to any free soluble rTNF that could have leaked out from the fixed rTNF cell preparations. The fixed rTNF cell preparations also stimulated the growth of human diploid fibroblasts, under conditions where little growth-stimulatory activity was found in suspension. These results indicate that TNF may exert its effect on target cells without internalization, perhaps through a receptor-mediated process that may alter the levels of a second messenger within the target cells. This signal transduction does not appear to involve cAMP or cGMP, since we were unable to detect significant changes in the levels of these two second messengers in TNF-exposed WEHI 164 clone 13 cells.
Hofsli
E
E
Institute of Cancer Research, University of Trondheim, Norway.
Nissen-Meyer
J
J
D002448:Cell Adhesion; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005404:Fixatives; D005557:Formaldehyde; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D011108:Polymers; D011994:Recombinant Proteins / Q000378:metabolism / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000633:toxicity*
D005404:Fixatives; D006133:Growth Substances; D011108:Polymers; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D000242:Cyclic AMP; D006152:Cyclic GMP; C003043:paraform