Houze T A, Larsson P A, Hellstrand K, Gustavsson B
Ostra Hospital, Molecular Oncology Laboratory, Gothenborg, Sweden.
Cell Biol Int. 1996 Sep;20(9):589-98. doi: 10.1006/cbir.1996.0077.
The secretion of interferon-gamma (IFN-gamma) by natural killer (NK) cells following in vitro stimulation with interleukin-2 (IL-2) is inhibited by co-incubation with autologous monocytes at a transcriptional level by more than sixty-fold. In this study, we investigate the nature of the inhibitory signal and particularly the role of reactive oxygen metabolites (ROMs). It was found that the inhibition of IFN-gamma was operating at a pre-translational level, this was indicated by the inability of CD 56(+)-enriched natural killer cells to accumulate IFN-gamma mRNA in the presence of elutriated monocytes. Both catalase, a scavenger of hydrogen peroxide and histamine, a biogenic amine which inhibits the generation of ROMs by monocytes, strongly abrogated the inhibition of IFN-gamma production. We thereby conclude that histamine behaves synergistically with IL-2 at a transcriptional level to induce IFN-gamma even in an admixture of NK cells and monocytes.
自然杀伤（NK）细胞在白细胞介素-2（IL-2）体外刺激后分泌的干扰素-γ（IFN-γ），在转录水平上与自体单核细胞共同孵育时受到抑制，抑制程度超过60倍。在本研究中，我们调查了抑制信号的性质，特别是活性氧代谢产物（ROMs）的作用。研究发现，IFN-γ的抑制作用在翻译前水平发挥作用，这表现为在存在淘洗单核细胞的情况下，富含CD 56(+)的自然杀伤细胞无法积累IFN-γ mRNA。过氧化氢清除剂过氧化氢酶和抑制单核细胞产生ROMs的生物胺组胺，均强烈消除了对IFN-γ产生的抑制作用。我们由此得出结论，组胺在转录水平上与IL-2协同作用，即使在NK细胞和单核细胞混合的情况下也能诱导IFN-γ产生。
