Hirabayashi T, Demertzis S, Schäfers J, Hoshino K, Nashan B
Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, Germany.
Transpl Int. 1996;9 Suppl 1:S293-5. doi: 10.1007/978-3-662-00818-8_72.
In ongoing chronic rejection after lung transplantation, alveolar interstitial fibrosis develops. However, little is known about the mechanisms involved. In order to investigate these mechanisms, expression of extracellular matrix molecules (ECM) (undulin, decorin, tenascin, laminin, and fibronectin) and cytokines [transforming growth factor (TGF)-beta 1, TGF-beta 3, platelet-derived growth factor (PDGF), and PDGF receptor] were semiquantitatively evaluated in chronically rejected lung allografts, using standard immunohistochemical techniques. Additionally, the presence of macrophages was analysed. The present study demonstrates an increased infiltration of macrophages with a concomitant upregulation of cytokines (TGF-beta 1, TGF-beta 3, and PDGF) and an increased deposition of ECM in chronic lung rejection. These cytokines have an important role in the stimulation of fibroblasts which are a major source of ECM. Upregulated expression of ECM in the alveolar interstitial space leads to alveolar malfunction by thickening of the wall and, thus, is one of the causative factors of respiratory dysfunction in chronic lung graft rejection.
在肺移植后的持续性慢性排斥反应中，会出现肺泡间质纤维化。然而，其中涉及的机制却鲜为人知。为了探究这些机制，采用标准免疫组织化学技术，对慢性排斥的肺同种异体移植物中细胞外基质分子（ECM）（内收蛋白、核心蛋白聚糖、腱生蛋白、层粘连蛋白和纤连蛋白）和细胞因子[转化生长因子（TGF）-β1、TGF-β3、血小板衍生生长因子（PDGF）和PDGF受体]的表达进行了半定量评估。此外，还分析了巨噬细胞的存在情况。本研究表明，在慢性肺排斥反应中，巨噬细胞浸润增加，同时细胞因子（TGF-β1、TGF-β3和PDGF）上调，ECM沉积增加。这些细胞因子在刺激成纤维细胞方面具有重要作用，而成纤维细胞是ECM的主要来源。肺泡间质空间中ECM表达上调会导致肺泡壁增厚，进而引起肺泡功能障碍，因此是慢性肺移植排斥反应中呼吸功能障碍的致病因素之一。
