Effects of irradiation on the release of growth factors from cultured bovine, porcine, and human endothelial cells.
Effects of irradiation on the release of growth factors from cultured bovine, porcine, and human endothelial cells.
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发表时间：
1989-09
期刊：
影响因子：
11.2
通讯作者：
L. Witte;Z. Fuks;A. Haimovitz-Friedman;I. Vlodavsky;D. Goodman;A. Eldor
中科院分区：
文献类型：
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作者：
L. Witte;Z. Fuks;A. Haimovitz-Friedman;I. Vlodavsky;D. Goodman;A. Eldor
研究了辐射对牛、猪和人来源的培养内皮细胞释放促有丝分裂因子的影响。尽管未辐照的对照显示出显著的背景活性，但单剂量辐照（20-60戈伊）导致生长因子活性释放的剂量相关性增加，通过条件培养基对3 T3小鼠成纤维细胞和作为靶细胞的未辐照内皮细胞的促有丝分裂作用来测量。血小板衍生生长因子受体的受体结合竞争试验显示，总促有丝分裂活性的12-28%是由于血小板衍生生长因子样促有丝分裂原。使用内皮细胞和特异性抗体介导的抑制试验的促有丝分裂试验表明，促有丝分裂活性的另一个组成部分是由于成纤维细胞生长因子样因子。虽然辐射导致细胞死亡的显着增加，增强生长因子的活动似乎并没有导致细胞溶解相关的泄漏的细胞内储存的生长因子。相反，我们的数据表明，生长因子是从头合成的，并由维持辐射后高水平代谢活性的细胞以升高的水平分泌。时程研究表明，在条件培养基中的生长因子的积累开始在辐射后的第一个24小时内，并在治疗后72小时内达到一个平台。辐射诱导的内皮细胞源性生长因子的释放可能参与早期血管损伤和晚期纤维化的发病机制，后者代表正常组织中晚期辐射损伤的显著特征。
The effects of radiation on the release of mitogenic factors into the media of cultured endothelial cells of bovine, porcine, and human origins were studied. Although unirradiated controls revealed a significant background activity, single doses of irradiation (20-60 Gy) resulted in a dose-related increased release of growth factor activity, measured by the mitogenic effects of the conditioned media on both 3T3 mouse fibroblasts and unirradiated endothelial cells serving as target cells. Receptor binding competition assays for the platelet-derived growth factor receptor revealed that 12-28% of the total mitogenic activity was due to platelet-derived growth factor-like mitogens. Mitogenic assays using endothelial cells and specific antibody mediated inhibition assays suggested that another component of the mitogenic activity was due to a fibroblast growth factor-like factor. Although radiation resulted in a significant increase in cell death, the enhanced growth factor activities did not appear to result from cell lysis-related leakage of intracellular stores of growth factor. Instead, our data suggest that the growth factors were synthesized de novo and secreted at elevated levels by the cells which maintained postradiation a high level of metabolic activity. Time course studies demonstrated that the growth factors accumulation in the conditioned media started within the first 24 h after radiation and reached a plateau within 72 h after treatment. Radiation-induced release of endothelial cell-derived growth factors may be involved in the pathogenesis of both early vascular damage and the late fibrosis which represents a prominent feature of late radiation damage in normal tissues.