The role of fibrocytes in sickle cell lung disease. PLoS One 2012;7(3):e33702
Date
03/24/2012Pubmed ID
22442712Pubmed Central ID
PMC3307761DOI
10.1371/journal.pone.0033702Scopus ID
2-s2.0-84863389833 (requires institutional sign-in at Scopus site) 21 CitationsAbstract
BACKGROUND: Interstitial lung disease is a frequent complication in sickle cell disease and is characterized by vascular remodeling and interstitial fibrosis. Bone marrow-derived fibrocytes have been shown to contribute to the pathogenesis of other interstitial lung diseases. The goal of this study was to define the contribution of fibrocytes to the pathogenesis of sickle cell lung disease.
METHODOLOGY/PRINCIPAL FINDINGS: Fibrocytes were quantified and characterized in subjects with sickle cell disease or healthy controls, and in a model of sickle cell disease, the NY1DD mouse. The role of the chemokine ligand CXCL12 in trafficking of fibrocytes and phenotype of lung disease was examined in the animal model. We found elevated concentration of activated fibrocytes in the peripheral blood of subjects with sickle cell disease, which increased further during vaso-occlusive crises. There was a similar elevations in the numbers and activation phenotype of fibrocytes in the bone marrow, blood, and lungs of the NY1DD mouse, both at baseline and under conditions of hypoxia/re-oxygenation. In both subjects with sickle cell disease and the mouse model, fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on most fibrocytes, and CCR2 and CCR7 expressed on a smaller subset of cells. Depletion of the CXCR4 ligand, CXCL12, in the mouse model resulted in a marked reduction of fibrocyte trafficking into the lungs, reduced lung collagen content and improved lung compliance and histology.
CONCLUSIONS: These data support the notion that activated fibrocytes play a significant role in the pathogenesis of sickle cell lung disease.
Author List
Field JJ, Burdick MD, DeBaun MR, Strieter BA, Liu L, Mehrad B, Rose CE Jr, Linden J, Strieter RMAuthor
Joshua J. Field MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAnemia, Sickle Cell
Animals
Cell Movement
Chemokine CXCL12
Collagen
Female
Humans
Lung Diseases, Interstitial
Male
Mice
Middle Aged
Pulmonary Fibrosis
Receptors, Chemokine
