Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis
Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis
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DOI：
10.1016/j.biocel.2008.02.012
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Selman, Moises
中科院分区：
文献类型：
--
作者：
Andersson-Sjoland, Annika;de Alba, Carolina Garcia;Selman, Moises
特发性肺纤维化的特征是成纤维细胞/肌成纤维细胞的积累和肺实质的异常重塑。然而，IPF肺中成纤维细胞的来源尚不清楚。纤维细胞是参与伤口愈合和纤维化的成纤维细胞的循环祖细胞。在这项研究中，我们通过免疫荧光和共聚焦显微镜评估了特发性肺纤维化患者肺中存在纤维细胞的证据。9例纤维化肺中有8例在组织中发现纤维细胞。与使用CD34或CD45RO与间充质标志物联合使用相比，CXCR4与间充质标志物联合使用可显著染色更多的纤维细胞/mm(2)组织：CXCR4/原胶原- i（10.3 +/- 2.9纤维细胞/mm(2)）和CXCR4/丙氨酸-4羟化酶（4.1 +/- 3.1），而CD34/原胶原- i (2.8 +/- 3.0), CD34/ α SMA（2.2 +/- 1.6）和CD45RO/丙氨酸-4羟化酶（1.3 +/- 1.6）；P < 0.003。成纤维细胞灶的丰度与肺纤维细胞的数量呈正相关（r=0.79; p < 0.02）。正常肺未见纤维细胞。血浆中纤维细胞引诱趋化因子CXCL12升高[中位数：2707.5 pg/ml(648.1-4884.7)，而健康对照组为1751.5 pg/ml (192.9-2686.0)；P < 0.003)]，并且在40%的患者的支气管肺泡灌洗液中检测到，而在对照组中未检测到。肺泡上皮细胞强烈表达CXCL12。血浆CXCL12水平与运动时肺一氧化碳弥散量（DLCO） （r=-0.56, p < 0.03）和氧饱和度（r=-0.41, p < 0.04）呈负相关。这些发现表明，循环纤维细胞，可能通过CXCR4/CXCL12轴募集，可能有助于特发性肺纤维化中成纤维细胞/肌成纤维细胞群的扩张。(C) 2008 Elsevier Ltd版权所有。
Idiopathic pulmonary fibrosis is characterized by the accumulation of fibroblasts/myofibroblasts and aberrant remodeling of the lung parenchyma. However, the sources of fibroblasts in IPF lungs are unclear. Fibrocytes are circulating progenitors of fibroblasts implicated in wound healing and fibrosis. In this study we evaluated evidence for the presence of fibrocytes in the lung of patients with idiopathic pulmonary fibrosis by immunofluorescence and confocal microscopy. Fibrocytes were identified in tissues in 8 out of 9 fibrotic lungs. Combinations including CXCR4 and a mesenchymal marker stained significantly more fibrocytes/mm(2) of tissue compared with combinations using CD34 or CD45RO with mesenchymal markers: CXCR4/procollagen-I (10.3 +/- 2.9 fibrocytes/mm(2)) and CXCR4/prolyl-4-hydroxylase (4.1 +/- 3.1), versus CD34/procollagen-I (2.8 +/- 3.0), CD34/alpha SMA (2.2 +/- 1.6) and CD45RO/prolyl-4-hydroxylase (1.3 +/- 1.6); p < 0.003. There was a positive correlation between the abundance of fibroblastic foci and the amount of lung fibrocytes (r=0.79; p < 0.02). No fibrocytes were identified in normal lungs. The fibrocyte attractant chemokine CXCL12 increased in plasma [median: 2707.5 pg/ml (648.1-4884.7) versus 1751.5 pg/ml (192.9-2686.0) from healthy controls; p < 0.003)] and was detectable in the bronchoalveolar lavage fluid of 40% of the patients but not in controls. In the lung CXCL12 was strongly expressed by alveolar epithelial cells. A negative correlation between plasma levels of CXCL12 with lung diffusing capacity for carbon monoxide (DLCO) (r=-0.56; p < 0.03) and oxygen saturation on exercise was found (r=-0.41; p < 0.04). These findings indicate that circulating fibrocytes, likely recruited through the CXCR4/CXCL12 axis, may contribute to the expansion of the fibroblast/myofibroblast population in idiopathic pulmonary fibrosis. (C) 2008 Elsevier Ltd. All rights reserved.