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Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms

gdlizhaokun 添加于 2009-7-3 23:17 | 1388 次阅读 | 3 个评论

作者
El-Chemaly S, Malide D, Zudaire E, Ikeda Y, Weinberg BA, Pacheco-Rodriguez G, Rosas IO, Aparicio M, Ren P, MacDonald SD, Wu H-P, Nathan SD, Cuttitta F, McCoy JP, Gochuico BR, Moss J
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.
详细资料
- 关键词: Antigens, CD11b/metabolism; Biological Markers/metabolism; Bronchoalveolar Lavage Fluid; Cell Movement/drug effects; Endothelial Cells/drug effects/metabolism/pathology; Health; Humans; Hyaluronic Acid/metabolism; Hyaluronoglucosaminidase/pharmacology; Idiopathic Pulmonary Fibrosis/*complications/*pathology; *Lymphangiogenesis/drug effects; Macrophages/drug effects/metabolism/pathology; Neovascularization, Physiologic/drug effects; Pulmonary Alveoli/metabolism/pathology; Vesicular Transport Prot
- 文献种类:期刊
- 期刊名称: Proceedings of the National Academy of Sciences of the United States of America
- 期刊缩写: Proc Natl Acad Sci U S A
- 期卷页: 2009年第106卷第10期 3958-3963页
- 地址: Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
- ISBN: 1091-6490
- 备注:PMID:19237567
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