Thornton S C, Walsh B J, Bennett S, Robbins J M, Foulcher E, Morgan G W, Penny R, Breit S N
Centre for Immunology, St Vincent's Hospital, Sydney, Australia.
Clin Exp Immunol. 1996 Jan;103(1):67-73. doi: 10.1046/j.1365-2249.1996.898598.x.
Fibrosis in the lung directly underlying the field of irradiation is an almost universal long term sequelae of thoracic irradiation. It is assumed to represent the consequence of direct damage to local tissues and/or vascular endothelium by ionizing radiation. This view, however, is not in keeping with our current understanding of fibrotic processes, which suggest that growth factors for fibroblasts (including platelet-derived growth factor (PDGF), insulin-like growth factor I (IGF-I)) and cytokines stimulating collagen synthesis (notably transforming growth factor-beta) are largely responsible for this process. Since a major source of these factors is the macrophage, present in large numbers within the lung, it appeared possible that radiation-induced fibrosis might be mediated by similar mechanisms. Therefore, a study was designed to determine, first, whether in vitro irradiation of mononuclear phagocytes could induce the release of growth factors for fibroblasts. Second, we wished to ascertain whether these same growth factors might also be secreted by bronchoalveolar cells from humans who had undergone in vivo thoracic irradiation. The results of this study indicate that irradiation of a number of different types of mononuclear phagocytes resulted in the dose-dependent synthesis and release of several growth factors for fibroblasts, including PDGF, tumour factor-alpha (TNF-alpha) and IGF-I. Further, cells obtained by bronchoalveolar lavage from patients undergoing thoracic radiation spontaneously released PDGF following irradiation. These findings strongly support the contention that synthesis and release of macrophage-derived growth factors for fibroblasts (particularly PDGF and IGF-I) occur after thoracic irradiation and play a significant role in the pathogenesis of irradiation-induced pulmonary fibrosis in humans.
照射野正下方肺组织的纤维化是胸部照射几乎普遍存在的长期后遗症。一般认为，这是电离辐射对局部组织和/或血管内皮直接损伤的结果。然而，这种观点与我们目前对纤维化过程的理解并不一致，目前的理解表明，成纤维细胞生长因子（包括血小板衍生生长因子（PDGF）、胰岛素样生长因子I（IGF-I））和刺激胶原蛋白合成的细胞因子（特别是转化生长因子-β）在很大程度上导致了这一过程。由于这些因子的主要来源是巨噬细胞，而巨噬细胞在肺内大量存在，因此辐射诱导的纤维化可能是由类似机制介导的。因此，设计了一项研究，首先确定体外照射单核吞噬细胞是否能诱导成纤维细胞生长因子的释放。其次，我们想确定这些相同的生长因子是否也可能由接受体内胸部照射的人的支气管肺泡细胞分泌。这项研究的结果表明，对多种不同类型的单核吞噬细胞进行照射会导致几种成纤维细胞生长因子的剂量依赖性合成和释放，包括PDGF、肿瘤坏死因子-α（TNF-α）和IGF-I。此外，接受胸部放疗患者支气管肺泡灌洗获得的细胞在照射后自发释放PDGF。这些发现有力地支持了以下观点，即胸部照射后会出现巨噬细胞衍生的成纤维细胞生长因子（特别是PDGF和IGF-I）的合成和释放，并且在人类辐射诱导的肺纤维化发病机制中起重要作用。
