Takashima T, Ohnishi K, Tsuyuguchi I, Kishimoto S
Osaka Prefectural Habikino Hospital, Habikino, Japan.
J Immunol. 1993 Apr 1;150(7):3002-10.
We found that in vitro multinucleated giant cells (MGC) could be produced by incubation of highly purified human blood monocytes with Con A alone, and the effect of Con A was dose- and time-dependent. Any of the cytokines considered as macrophage-activating factor, such as IFN-gamma, IL-2, IL-4, GM-CSF, or TNF-alpha, did not induce MGC by itself. When added to monocyte cultures, however, IFN-gamma enhanced Con A-induced MGC formation in a dose-dependent manner. In contrast, IL-4 suppressed this response in a dose- and time-dependent manner. IL-4 antagonized the enhancing effect of IFN-gamma on Con A-induced MGC formation. This ability to suppress the formation of MGC was completely abrogated after treatment with anti-IL-4 antibody. In addition, the involvement of monokines (IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha) in Con A-induced monocyte fusion was investigated by adding various antimonokine polyclonal antibodies in cultures. Normal rabbit IgG, anti-IL-1 alpha rabbit antibody, and anti-IL-1 beta rabbit antibody had no effect on Con A-induced MGC formation. However, anti-TNF-alpha rabbit antibody had suppressed the monocyte fusion induced by Con A in a dose-dependent manner, and a high dose of anti-IL-6 rabbit antibody had a partially suppressive effect. Anti-TNF-alpha mAb also had an inhibitory effect on monocyte fusion. Furthermore, the enhancing effect of IFN-gamma on this response was entirely abrogated by anti-TNF-alpha rabbit antibody. There was a highly significant positive correlation between the fusion rates of monocytes and the levels of TNF-alpha produced by monocytes (r = 0.68, p < 0.0005). Our results indicate that T cell-derived lymphokines, such as IFN-gamma and IL-4, have mutually antagonistic effects on Con A-induced human MGC formations in vitro, in which the expression of TNF-alpha in human monocytes plays a key role in the fusion process of monocytes.
我们发现，通过将高度纯化的人血单核细胞单独与刀豆蛋白A（Con A）孵育，可在体外产生多核巨细胞（MGC），且Con A的作用具有剂量和时间依赖性。任何被视为巨噬细胞激活因子的细胞因子，如干扰素-γ（IFN-γ）、白细胞介素-2（IL-2）、白细胞介素-4（IL-4）、粒细胞-巨噬细胞集落刺激因子（GM-CSF）或肿瘤坏死因子-α（TNF-α），自身均不能诱导MGC形成。然而，当添加到单核细胞培养物中时，IFN-γ以剂量依赖性方式增强Con A诱导的MGC形成。相反，IL-4以剂量和时间依赖性方式抑制这种反应。IL-4拮抗IFN-γ对Con A诱导的MGC形成的增强作用。在用抗IL-4抗体处理后，这种抑制MGC形成的能力被完全消除。此外，通过在培养物中添加各种抗单核因子多克隆抗体，研究了单核因子（IL-1α、IL-1β、IL-6和TNF-α）在Con A诱导的单核细胞融合中的作用。正常兔免疫球蛋白（IgG）、抗IL-1α兔抗体和抗IL-1β兔抗体对Con A诱导的MGC形成没有影响。然而，抗TNF-α兔抗体以剂量依赖性方式抑制Con A诱导的单核细胞融合，高剂量的抗IL-6兔抗体具有部分抑制作用。抗TNF-α单克隆抗体（mAb）对单核细胞融合也有抑制作用。此外，抗TNF-α兔抗体完全消除了IFN-γ对这种反应的增强作用。单核细胞的融合率与单核细胞产生的TNF-α水平之间存在高度显著的正相关（r = 0.68，p < 0.0005）。我们的结果表明，T细胞衍生的淋巴因子，如IFN-γ和IL-4，在体外对Con A诱导的人MGC形成具有相互拮抗作用，其中人单核细胞中TNF-α的表达在单核细胞的融合过程中起关键作用。
