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本文研究了重组人转化生长因子-β1对前单核白血病细胞系THP-1细胞增殖抑制作用和分化诱导作用。细胞染色计数和~3H-TdR掺入数据表明,在0.078—1.25 ng/ml浓度范围内,rhTGF-β1剂量与增殖抑制呈正相关。在抑制细胞增殖的同时,rhTGF-β1诱导细胞分化,诱导体系中细胞形态和生长方式均发生明显变化,细胞转为贴壁生长,表现出Mφ的细胞形态。α-醋酸萘酚酯酶、硝基蓝四唑还原、细胞吞噬试验均表明细胞具有Mφ的生物功能。电镜观察显示分化细胞具有典型的巨噬细胞样细胞形态,胞内出现Mφ所特有的亚细胞结构初级溶酶体和次级溶酶体。另外,TGF-β特异性中和单抗TB 21对实验体系THP-1细胞分化的阻断证明,THP-1细胞的分化确为rhTGF-β1诱导所致。
In this study, we investigated the inhibitory and proliferation-inducing effects of recombinant human transforming growth factor-β1 on THP-1 cells. The data of cell staining and ~3H-TdR incorporation showed that rhTGF-β1 dose was positively correlated with proliferation inhibition in the range of 0.078-1.25 ng/ml. While inhibiting cell proliferation, rhTGF-β1 induced cell differentiation. The cell morphology and growth patterns in the induced system all changed significantly, and the cells turned to adherent growth, showing the cell morphology of Mφ. The α-acetate naphthol esterase, nitroblue tetrazolium reduction, and cell phagocytosis tests showed that the cells have the biological function of Mφ. Electron microscopic observations showed that the differentiated cells had typical macrophage-like cell morphology, and the subcellular primary lysosomes and secondary lysosomes characteristic of Mφ were found intracellularly. In addition, the blocking of the differentiation of THP-1 cells in the experimental system by TGF-β-specific neutralizing monoclonal antibody TB 21 demonstrated that the differentiation of THP-1 cells was indeed caused by the induction of rhTGF-β1.