Nissen-Meyer J, Hofsli E, Espevik T, Austgulen R
Institute of Cancer Research, University of Trondheim, Regionsykehuset, Norway.
Nat Immun Cell Growth Regul. 1988;7(5-6):266-79.
Human monocytes cultured in a specially prepared medium free of lipopolysaccharide (LPS) constitutively produced a small, though significant, amount of tumor necrosis factor (TNF). Upon addition of LPS, the amount produced remained constant until the LPS concentration reached 1-10 ng/ml, whereupon the production of TNF dramatically increased, eventually becoming 100-fold greater than when the LPS concentration was below 1 ng/ml. Priming the monocytes with recombinant interferon-gamma (rIFN-gamma) before LPS exposure resulted in a 2- to 10-fold increase in TNF production, the highest relative increase being obtained at lower LPS concentrations and in the absence of LPS. Monocyte-produced TNF appears to be the effector molecule in monocyte-mediated killing of some target cell types, since antiserum against recombinant TNF inhibited killing of both actinomycin D-treated and untreated WEHI 164 cells by human monocytes. However, it also appears that TNF may not in all cases be an effector molecule in monocyte-mediated killing, since cytolysis of K562 cells mediated by IFN-gamma/LPS-activated monocytes was not inhibited by antiserum against recombinant TNF. Antiserum which was raised against a monocyte-derived cytotoxic factor and which neutralized recombinant TNF did, however, inhibit monocyte-mediated cytolysis of K562 cells, suggesting that an extracellular factor, perhaps related to TNF, was also involved in monocyte-mediated killing of K562 cells. A TNF-like activity was associated with the monocyte surface membrane, since paraformaldehyde-fixed monocytes expressed cytotoxic activity which was neutralized by antiserum against recombinant TNF. Fixed monocytes activated with rIFN-gamma in addition to LPS before fixation were generally more cytotoxic than those exposed to LPS alone, and those exposed to LPS were much more cytotoxic than those not exposed to LPS. Thus it is possible that high local TNF concentrations may be generated near the target cell upon direct contact between effector and target cells, and that also monocyte-associated TNF may in this way be involved in monocyte-mediated cytotoxicity.
在特别制备的不含脂多糖（LPS）的培养基中培养的人单核细胞，组成性地产生少量但显著量的肿瘤坏死因子（TNF）。加入LPS后，TNF产生量保持恒定，直到LPS浓度达到1 - 10 ng/ml，此时TNF的产生量急剧增加，最终比LPS浓度低于1 ng/ml时高出100倍。在LPS暴露前用重组干扰素-γ（rIFN-γ）预处理单核细胞，导致TNF产生量增加2至10倍，在较低LPS浓度和无LPS的情况下获得的相对增加最高。单核细胞产生的TNF似乎是单核细胞介导的对某些靶细胞类型杀伤的效应分子，因为抗重组TNF的抗血清抑制了人单核细胞对放线菌素D处理和未处理的WEHI 164细胞的杀伤。然而，似乎TNF在所有情况下可能并非单核细胞介导杀伤的效应分子，因为抗重组TNF的抗血清并未抑制IFN-γ/LPS激活的单核细胞介导的K562细胞的细胞溶解。然而，针对单核细胞衍生的细胞毒性因子产生的并中和重组TNF的抗血清确实抑制了单核细胞介导的K562细胞的细胞溶解，表明一种可能与TNF相关的细胞外因子也参与了单核细胞介导的K562细胞杀伤。一种TNF样活性与单核细胞表面膜相关，因为多聚甲醛固定的单核细胞表达的细胞毒性活性被抗重组TNF的抗血清中和。在固定前用rIFN-γ和LPS共同激活的固定单核细胞通常比单独暴露于LPS的细胞更具细胞毒性，而暴露于LPS的细胞比未暴露于LPS的细胞细胞毒性大得多。因此，效应细胞与靶细胞直接接触时，有可能在靶细胞附近产生高局部TNF浓度，并且单核细胞相关的TNF也可能以这种方式参与单核细胞介导的细胞毒性作用。
