Mockridge J W, Carter C, Holder A T
The Babraham Institute, Cambridge, UK.
Horm Metab Res. 1998 Oct;30(10):610-3. doi: 10.1055/s-2007-978943.
Investigations into the mechanism underlying antibody-mediated enhancement of growth hormone action have been hampered by the lack of an in vitro assay system. In this work, we have used isolated ovine costal cartilage growth plate chondrocytes to demonstrate, for the first time, that monoclonal antibody EB1 can enhance the proliferative actions of human growth hormone on this cell type. Chondrocytes were cultured for 14 days prior to exposure to GH+/-monoclonal antibody EB1 for a 4-day treatment period. Human growth hormone alone promoted a significant dose-dependent increase in chondrocyte proliferation; maximal stimulation was achieved at about 3.3-10 ng/ml growth hormone, and at higher doses of growth hormone, the response declined. Monoclonal antibody EB1 was shown to enhance the proliferative activity of 10 ng/ml human growth hormone in a significant dose dependent fashion. In conclusion, our results demonstrate that an antibody capable of enhancing GH activity in vivo also has the capacity to potentiate GH activity in vitro. This system may provide an important tool for investigations into the mechanism of GH action, and how this is modified by GH enhancing MAbs.
由于缺乏体外检测系统，对抗体介导的生长激素作用增强机制的研究受到了阻碍。在这项研究中，我们首次使用分离的绵羊肋软骨生长板软骨细胞，证明单克隆抗体EB1能够增强人生长激素对这种细胞类型的增殖作用。在暴露于生长激素±单克隆抗体EB1进行4天治疗期之前，软骨细胞先培养14天。单独的人生长激素可促进软骨细胞增殖显著的剂量依赖性增加；在约3.3 - 10 ng/ml生长激素时达到最大刺激，而在更高剂量的生长激素下，反应下降。单克隆抗体EB1以显著的剂量依赖性方式增强10 ng/ml人生长激素的增殖活性。总之，我们的结果表明，一种能够在体内增强生长激素活性的抗体在体外也具有增强生长激素活性的能力。该系统可能为研究生长激素作用机制以及生长激素增强单克隆抗体如何改变该机制提供重要工具。
