Antitransforming growth factor-β antibody 1D11 ameliorates normal tissue damage caused by high-dose radiation
Antitransforming growth factor-β antibody 1D11 ameliorates normal tissue damage caused by high-dose radiation
复制标题
DOI：
10.1016/j.ijrobp.2006.02.051
复制
发表时间：
2006-07-01
影响因子：
7
通讯作者：
Vujaskovic, Z
中科院分区：
文献类型：
--
作者：
Anscher, MS;Thrasher, B;Vujaskovic, Z
目的：本研究的目的是确定是否中和转化生长因子-β（TGF β）抗体可以防止辐射（RT）诱导的肺injury.Methods和Materials：Fractionated和假右肺照射Fischer 344大鼠进行评估的抗辐射效果。将动物分成以下组：（1）对照（假RT，对照抗体13 C4）;（2）RT（800 cGy X 5）+13C4）;（3）RT +0. lmg/kg 1D 11抗TGF β抗体;和（4）RT + lmg/kg 1D 11抗体。在RT的最后一部分后立即腹膜内施用抗体。在照射后6周和26周处死动物。评估肺的组织学变化、巨噬细胞的活化、TGF β的表达/活化及其信号转导通路。RT后6周，巨噬细胞聚集显著减少，接受1.0 mg/kg 1D 11的动物与对照组相比，肺泡壁厚度（p = 0.0003）和TGF-β活化（p = 0.032）。然而，在6周时，低剂量的1D 11抗体（0.1 mg/kg）未能产生任何显著变化。在RT后6个月，接受1.0 mg/kg 1D 11的组的放射保护作用明显，具有活化的巨噬细胞（p = 0.037），肺泡壁厚度（p = 0.0002），TGF β活化（p = 0.002）及其信号转导蛋白与对照组比较，P < 0.05。施用单剂量1.0 mg/kg的抗TGF β抗体1D 11导致形态学变化、炎症反应在40戈伊照射后6周和6个月，右半胸TGF β的表达和活化减少。靶向TGF β通路可能是预防辐射诱导的肺损伤的有用策略。(c)2006年爱思唯尔公司
Purpose: The aim of this study was to determine whether a neutralizing transforming growth factor-beta (TGF beta) antibody can prevent radiation (RT) induced lung injury.Methods and Materials: Fractionated and sham right lung irradiation in Fischer 344 rats was delivered to assess the radioprotective effect of the antibodies. Animals were divided into the following groups: (1) control (sham RT, control antibody 13C4); (2) RT (800cGy x 5)+13C4); (3) RT + 0.1 mg/kg 1D11 anti-TGF beta antibody; and (4) RT + 1 mg/kg 1D11 antibody. Antibodies were intraperitoneally administered immediately after the last fraction of RT. Animals were sacrificed at 6 and 26 weeks after irradiation. Lungs were assessed for histologic changes, activation of macrophages, expression/activation of TGF beta and its signal transduction pathway.Results: At 6 weeks post-RT, there was a significant reduction in macrophage accumulation (p = 0.041), alveolar wall thickness (p = 0.0003), and TGF-beta activation (p = 0.032) in animals receiving 1.0 mg/kg 1D11 vs. in the control group. However, at 6 weeks, the low dose of 1D11 antibody (0.1 mg/kg) failed to produce any significant changes. At 6 months post-RT, radioprotection is apparent for the group receiving 1.0 mg/kg 1D11, with activated macrophages (p = 0.037), alveolar wall thickness (p = 0.0002), TGF beta activation (p = 0.002) and its signal transduction proteins (p < 0.05) compared with the control group.Conclusions: Administration of a single dose of 1.0 mg/kg of the anti-TGF beta antibody 1D11 resulted in decreased morphologic changes, inflammatory response, and reduced expression and activation of TGF beta 6 weeks and 6 months after 40 Gy to the right hemithorax. Targeting the TGF beta pathway may be a useful strategy to prevent radiation-induced lung injury. (c) 2006 Elsevier Inc.