Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis

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• 作者：Annika Andersson-Sjö ; l ; Carolina Garcí ; a de Alba ; Kristian Nihlberg ; Carina Becerril ; Remedios Ramí ; rez ; Annie Pardo ; Gunilla Westergren-Thorsson ; Moisé ; s Selman
• 关键词：Pulmonary fibrosis ; Fibrocytes ; Fibroblasts ; CXCL12 ; Fibroblastic foci
• 刊名：The International Journal of Biochemistry and Cell Biology
• 出版年：2008
• 出版时间：2008
• 年：2008
• 卷：40
• 期：10
• 页码：2129-2140
• 全文大小：1435 K

文摘

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/mm² of tissue compared with combinations using CD34 or CD45RO with mesenchymal markers: CXCR4/procollagen-I (10.3 ± 2.9 fibrocytes/mm²) and CXCR4/prolyl-4-hydroxylase (4.1 ± 3.1), versus CD34/procollagen-I (2.8 ± 3.0), CD34/αSMA (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.