the role of fibrocytes in sickle cell lung disease肺纤维细胞在镰状细胞病的作用.pdfVIP

The Role of Fibrocytes in Sickle Cell Lung Disease 2 1 3 1 1 1 Joshua J. Field , Marie D. Burdick , Michael R. DeBaun , Brett A. Strieter , Ling Liu , Borna Mehrad , 1 4 1 C. Edward Rose, Jr. , Joel Linden , Robert M. Strieter * 1 Department of Medicine, Division of Pulmonary and Critical Care Medicine, The University of Virginia School of Medicine, Charlottesville, Virginia, United States of America, 2 Blood Center of Wisconsin, Blood Research Institute, Milwaukee, Wisconsin, United States of America, 3 Departments of Pediatrics and Medicine, Division of Hematology and Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America, 4 La Jolla Institute for Allergy Immunology, La Jolla, California, United States of America 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. 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 periphera