Circulating Fibrocytes Are Increased in Neonates with Bronchopulmonary Dysplasia.
BACKGROUND
Bronchopulmonary dysplasia (BPD) is characterized by the aberrant remodeling of the lung parenchyma, resulting from accumulation of fibroblasts or myofibroblasts. Circulating fibrocytes are implied in pulmonary fibrosis, but whether these cells are associated with the development of BPD or the progressive fibrosis is unknown. The aim of the present study was to investigate the occurrence of fibrocytes in peripheral venous blood and explore whether these cells might be associated with severity of BPD.


METHODS
We investigated circulating fibrocytes in 66 patients with BPD, 23 patients with acute respiratory distress syndrome(ARDS) and 11 normal subjects. Circulating fibrocytes were defined and quantified as cells positive for CD45 andcollagen-1 by flow cytometry. Furthermore, serum SDF-1/CXCL12 and TGF-β1 were evaluated using ELISA methods. We also investigated the clinical value of fibrocyte counts by comparison with standard clinical parameters.


RESULTS
The patients with BPD had significantly increased numbers of fibrocytes compared to the controls (p < 0.01). Patients with ARDS were not different from healthy control subjects. There was a correlation between the number of fibrocytes and pulmonary hypertension or oxygen saturation (p < 0.05). Fibrocyte numbers were not correlated with other clinical or functional variables or radiologic severity scores. The fibrocyte attractant chemokine CXCL12 increased in plasma (p < 0.05) and was detectable in the bronchoalveolar lavage fluid of 40% of the patients but not in controls.


CONCLUSIONS
These findings indicate that circulating fibrocytes are increased in patients with BPD and may contribute to pulmonary fibrosis in BPD. Circulating fibrocytes, likely recruited through the CXCR4/CXCL12 axis, might contribute to the production of TGF-β1 for the expansion of fibroblast/myofibroblast population in BPD.
Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Chun
C
Li
Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.
Xiaoyu
X
Li
Department of Neonatology, Children's Hospital of Chongqing Medical University, Chongqing, China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's hospital, Chongqing Medical University, Chongqing, 400014, P.R. China.
Chun
C
Deng
Department of Pediatric General Surgery and Liver Transplantation, Children's hospital, Chongqing Medical University, Chongqing, 400014, P.R. China.|Ministry of Education Key Laboratory of Child Development and Disorders, Children's hospital, Chongqing Medical University, Chongqing, 400014, P.R. China.
Chunbao
C
Guo
D001997:Bronchopulmonary Dysplasia / Q000097:blood* / Q000473:pathology; D054377:Chemokine CXCL12 / Q000097:blood*; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000097:blood* / Q000473:pathology; D019718:Receptors, CXCR4 / Q000097:blood*; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000097:blood*
C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D053773:Transforming Growth Factor beta1