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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Abnormal Lymphangiogenesis In Idiopathic Pulmonary Fibrosis With Insights Into Cellular And Molecular Mechanisms
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Abnormal Lymphangiogenesis In Idiopathic Pulmonary Fibrosis With Insights Into Cellular And Molecular Mechanisms

机译：特发性肺纤维化中异常淋巴管生成的细胞和分子机制研究

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摘要

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis is poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis is part of lung remodeling and sought to characterize pathways leading to lymphangiogenesis in IPF. We found that the diameter of lymphatic vessels in alveolar spaces in IPF lung tissue correlated with disease severity, suggesting that the alveolar microenvironment plays a role in the lymphangiogenic process. In bronchoalveolar lavage fluid (BALF) from subjects with IPF, we found short-fragment hyaluronic acid, which induced migration and proliferation of lymphatic endothelial cells (LECs), processes required for lymphatic vessel formation. To determine the origin of LECs in IPF, we isolated macrophages from the alveolar spaces; CD11b~+ macrophages from subjects with IPF, but not those from healthy volunteers, formed lymphatic-like vessels in vitro. Our findings demonstrate that in the alveolar microenvironment of IPF, soluble factors such as short-fragment hyaluronic acid and cells such as CD11b~+ macrophages contribute to lymphangiogenesis. These results improve our understanding of lymphangiogenesis and tissue remodeling in IPF and perhaps other fibrotic diseases as well.
机译：特发性肺纤维化（IPF）是一种慢性，进行性，使人衰弱的呼吸系统疾病，其发病机理尚不清楚。在IPF中，肺实质进行了广泛的重塑。我们假设淋巴管生成是肺重构的一部分，并试图表征导致IPF中淋巴管生成的途径。我们发现IPF肺组织的肺泡间隙中淋巴管的直径与疾病的严重程度相关，这表明肺泡微环境在淋巴管生成过程中起作用。在患有IPF的受试者的支气管肺泡灌洗液（BALF）中，我们发现了短片段透明质酸，它诱导了淋巴管内皮细胞（LEC）的迁移和增殖，这是淋巴管形成所必需的过程。为了确定IPC中LEC的起源，我们从肺泡腔中分离出了巨噬细胞。 IPF受试者的CD11b〜+巨噬细胞，而不是健康志愿者的CD11b +，在体外形成了淋巴样血管。我们的发现表明，在IPF的肺泡微环境中，可溶性因子（例如短片段透明质酸）和CD11b〜+巨噬细胞等细胞有助于淋巴管生成。这些结果提高了我们对IPF以及其他纤维化疾病中淋巴管生成和组织重塑的理解。

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