The Role of Fibrocytes in Sickle Cell Lung Disease
| Autor: | Joel Linden, Robert M. Strieter, Michael R. DeBaun, Joshua J. Field, Ling Liu, C. Edward Rose, Marie D. Burdick, Brett A. Strieter, Borna Mehrad |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Anatomy and Physiology Pulmonology Pulmonary Fibrosis lcsh:Medicine Anemia Sickle Cell Cardiovascular CXCR4 Pathogenesis Mice Chemokine receptor Autosomal Recessive Cell Movement Immune Physiology Fibrocyte Pulmonary fibrosis Genetics medicine Animals Humans lcsh:Science Biology Clinical Genetics Multidisciplinary Lung business.industry lcsh:R Interstitial lung disease Human Genetics Hematology Middle Aged medicine.disease Chemokine CXCL12 Hemoglobinopathies medicine.anatomical_structure Immunology Medicine Female Receptors Chemokine lcsh:Q Collagen Bone marrow Lung Diseases Interstitial business Research Article |
| Zdroj: | PLoS ONE, Vol 7, Iss 3, p e33702 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0033702 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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