Fibrogenesis in alcoholic chronic pancreatitis:: the role of tissue necrosis, macrophages, myofibroblasts and cytokines
Fibrogenesis in alcoholic chronic pancreatitis:: the role of tissue necrosis, macrophages, myofibroblasts and cytokines
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DOI：
10.1038/modpathol.3800613
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发表时间：
2006-08-01
期刊：
影响因子：
7.5
通讯作者：
Kloeppel, Guenter
中科院分区：
文献类型：
--
作者：
Detlefsen, Soenke;Sipos, Bence;Kloeppel, Guenter
已发现肌成纤维细胞和细胞因子如转化生长因子-β 1（TGF-β 1）和血小板衍生生长因子（PDGF）-B在胰腺炎相关的纤维形成中起重要作用。然而，目前还不清楚炎症胰腺中的何处以及何时可以检测到这些纤维化细胞和细胞因子。在这项研究中，我们检查了酒精性慢性胰腺炎患者的胰腺组织，以确定肌成纤维细胞的定位和分布以及与组织损伤和炎症过程活性相关的细胞因子的表达。从59例酒精性慢性胰腺炎患者的胰腺标本组织中，炎症过程进行了组织学分期。肌成纤维细胞和细胞因子潜伏期相关肽，TGF-β前肽，TGF-β受体II，PDGF-B和PDGF受体的α-亚型进行了免疫组化鉴定，在10个选定的情况下，代表了四个定义阶段的酒精性慢性胰腺炎。在I期，即明显组织损伤的阶段，肌成纤维细胞数量众多，尤其与坏死区域周围的巨噬细胞相关。在II期，即细胞纤维化阶段，肌成纤维细胞是小叶间组织的主要成分。在III期，致密纤维化的阶段，肌成纤维细胞是罕见的，在IV期，当结石存在时，肌成纤维细胞仅检测到邻近由结石引起的导管溃疡。潜伏相关肽和TGF-β受体II以及PDGF-B和PDGF受体-α主要由I期和II期的巨噬细胞、肌成纤维细胞和上皮细胞表达。结果表明，酒精性慢性胰腺炎中的纤维化过程是由组织损伤后巨噬细胞和肌成纤维细胞的基于精氨酸的相互作用启动的。
Myofibroblasts and cytokines such as transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived growth factor (PDGF)-B have been found to play an important role in pancreatitis-associated fibrogenesis. It is still unclear, however, where in the inflamed pancreas and when these fibrogenic cells and cytokines can be detected. In this study we examined pancreatic tissue from patients with alcoholic chronic pancreatitis to determine the localization and distribution of myofibroblasts and the expression of cytokines in relation to the tissue damage and the activity of the inflammatory process. In tissue from pancreatic specimens from 59 patients with alcoholic chronic pancreatitis the inflammatory process was histologically staged. Myofibroblasts and the cytokines latency-associated peptide, a TGF-beta propeptide, TGF-beta receptor II, PDGF-B and the alpha-isoform of the PDGF receptor were immunohistochemically identified in 10 selected cases representing the four defined stages of alcoholic chronic pancreatitis. In stage I, the stage with overt tissue injury, myofibroblasts were numerous and especially associated with macrophages around areas of necrosis. In stage II, the stage with cellular fibrosis, myofibroblasts were the main component of the interlobular tissue. In stage III, the stage with dense fibrosis, myofibroblasts were rare, and in stage IV, when calculi were present, myofibroblasts were only detected adjacent to duct ulcerations caused by calculi. Latency-associated peptide and TGF-beta receptor II as well as PDGF-B and PDGF receptor-alpha were mainly expressed by macrophages, myofibroblasts and epithelial cells in stages I and II. The results suggest that the fibrogenic process in alcoholic chronic pancreatitis is initiated by a cytokine-based interplay of macrophages and myofibroblasts that follows tissue injury.