title: The role of fibrocytes in sickle cell lung disease.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Blood Center of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, United States of America.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Field
authors.forename: Marie D
authors.initials: MD
authors.lastname: Burdick
authors.forename: Michael R
authors.initials: MR
authors.lastname: DeBaun
authors.forename: Brett A
authors.initials: BA
authors.lastname: Strieter
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Borna
authors.initials: B
authors.lastname: Mehrad
authors.forename: C Edward
authors.initials: CE
authors.lastname: Rose
authors.forename: Joel
authors.initials: J
authors.lastname: Linden
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005260:Female; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D019707:Receptors, Chemokine / Q000378:metabolism
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019707:Receptors, Chemokine; D003094:Collagen