The Disappearance of Subpleural and Interlobular Lymphatics in Idiopathic Pulmonary Fibrosis
The Disappearance of Subpleural and Interlobular Lymphatics in Idiopathic Pulmonary Fibrosis
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DOI：
10.1089/lrb.2010.0008
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发表时间：
2010-01-01
影响因子：
1.4
通讯作者：
Nukiwa, Toshihiro
中科院分区：
文献类型：
--
作者：
Ebina, Masahito;Shibata, Naoko;Nukiwa, Toshihiro
背景：小叶间和胸膜下实质中的淋巴管有助于肺泡的清除，但在特发性肺纤维化肺中，这些淋巴管的重构信息非常有限，这些区域含有严重的纤维化。方法与结果：对18例特发性肺纤维化患者(手术活检10例，尸检8例)、6例机化性肺炎、6例细胞性非特异性间质性肺炎和5例正常对照的肺组织标本进行免疫组织化学染色和形态计量学分析。此外，还对淋巴管的三维重建、淋巴管内皮细胞的凋亡以及淋巴管生成生长因子的细胞进行了评估。特发性肺纤维化肺的胸膜下淋巴管和小叶间淋巴管在严重的纤维结缔组织病变中均明显减少，淋巴管生成稀少。特发性肺纤维化的胸膜下淋巴管的三维图像清楚地显示了纤维化的破坏；在这些淋巴管内皮细胞中观察到了凋亡。相反，机化性肺炎和细胞性非特异性间质性肺炎保留了这些淋巴管，肺泡内淋巴管生成活跃。结论：这些结果揭示了特发性肺纤维化肺的胸膜下淋巴管和小叶间淋巴管的严重损害，提示肺泡清除障碍是其难治性的另一个发病机制。
Background: The lymphatics in the interlobular and subpleural parenchyma contribute to alveolar clearance in the lung, but the information on the remodeling of these lymphatics is quite limited in idiopathic pulmonary fibrosis lungs that contain severe fibrosis in these regions. We compared the alteration of these lymphatics and lymphangiogenesis among idiopathic pulmonary fibrosis and nonfibrotic interstitial pneumonias with a better prognosis.Methods and Results: The lung tissue specimens of eighteen patients with idiopathic pulmonary fibrosis (ten surgical biopsies and eight autopsies), six with organizing pneumonia, six with cellular nonspecific interstitial pneumonia, and five normal controls were examined by morphometric analysis of the lymphatics identified by immunohistochemistry. In addition, three-dimensional reconstruction of lymphatics, apoptosis of lymphatic endothelial cells and the cells producing growth factors for lymphangiogenesis were also evaluated. Both the subpleural and the interlobular lymphatics in idiopathic pulmonary fibrosis lungs were significantly decreased in the severe fibroconnective lesions, with rare lymphangiogenesis. The three-dimensional images of the subpleural lymphatics in idiopathic pulmonary fibrosis clearly revealed destruction by fibrosis; apoptosis was observed in these lymphatic endothelial cells. In contrast, organizing pneumonia and cellular nonspecific interstitial pneumonia preserved these lymphatics, and active lymphangiogenesis occurred in the alveolar lesions.Conclusions: These results reveal severe damage of the subpleural and interlobular lymphatics in idiopathic pulmonary fibrosis lungs, and suggest impaired alveolar clearance as another pathogenesis of its refractoriness.