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

Andersson-Sjöland, Annika; de Alba, Carolina García; Nihlberg, Kristian LU ; Becerril, Carina; Ramírez, Remedios; Pardo, Annie; Westergren-Thorsson, Gunilla LU and Selman, Moisés (2008) In International Journal of Biochemistry & Cell Biology 40. p.2129-2140
Abstract
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... (More)
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+/-2.9fibrocytes/mm(2)) and CXCR4/prolyl-4-hydroxylase (4.1+/-3.1), versus CD34/procollagen-I (2.8+/-3.0), CD34/alphaSMA (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: 2707.5pg/ml (648.1-4884.7) versus 1751.5pg/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. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
International Journal of Biochemistry & Cell Biology
volume
40
pages
2129 - 2140
publisher
Elsevier
external identifiers
  • wos:000258479700019
  • pmid:18374622
  • scopus:48949117344
ISSN
1878-5875
DOI
10.1016/j.biocel.2008.02.012
language
English
LU publication?
yes
id
db127d01-b692-491c-9a10-7cd02df1531d (old id 1147967)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18374622?dopt=Abstract
date added to LUP
2008-05-08 08:46:09
date last changed
2017-07-09 04:36:07
@article{db127d01-b692-491c-9a10-7cd02df1531d,
  abstract     = {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+/-2.9fibrocytes/mm(2)) and CXCR4/prolyl-4-hydroxylase (4.1+/-3.1), versus CD34/procollagen-I (2.8+/-3.0), CD34/alphaSMA (2.2+/-1.6) and CD45RO/prolyl-4-hydroxylase (1.3+/-1.6); p&lt;0.003. There was a positive correlation between the abundance of fibroblastic foci and the amount of lung fibrocytes (r=0.79; p&lt;0.02). No fibrocytes were identified in normal lungs. The fibrocyte attractant chemokine CXCL12 increased in plasma [median: 2707.5pg/ml (648.1-4884.7) versus 1751.5pg/ml (192.9-2686.0) from healthy controls; p&lt;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&lt;0.03) and oxygen saturation on exercise was found (r=-0.41; p&lt;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.},
  author       = {Andersson-Sjöland, Annika and de Alba, Carolina García and Nihlberg, Kristian and Becerril, Carina and Ramírez, Remedios and Pardo, Annie and Westergren-Thorsson, Gunilla and Selman, Moisés},
  issn         = {1878-5875},
  language     = {eng},
  pages        = {2129--2140},
  publisher    = {Elsevier},
  series       = {International Journal of Biochemistry & Cell Biology},
  title        = {Fibrocytes are a potential source of lung fibroblasts in idiopathic pulmonary fibrosis.},
  url          = {http://dx.doi.org/10.1016/j.biocel.2008.02.012},
  volume       = {40},
  year         = {2008},
}