title: Bone Marrow-Derived Cells in the Pathogenesis of Lung Fibrosis.
abstract: Progressive pulmonary fibrosis is characterized by failed alveolar reepithelialization and fibroblast/myofibroblast accumulation, with deposition of extracellular matrix. This results in loss of lung elasticity, alveolar collapse and fibrosis, impaired gas exchange and progressive decline in pulmonary function. Myofibroblasts represent an activated, contractile cellular phenotype that are potent producers of collagen and other extracellular matrix proteins. It is generally thought that myofibroblasts derive from local tissue fibroblasts. However, recent evidence suggests a portion of the progenitors for these cells may arise from the bone marrow. Fibrocytes, which share both leukocyte and mesenchymal markers, are found in increased numbers in bone marrow and lung of injured mice. Fibrocytes circulate in blood and are recruited to injured sites via chemotactic signals. Studies with bone marrow chimeric and parabiotic mice suggest that fibroblasts (and in some cases myofibroblasts) arise from circulating bone marrow precursors. Chemokine and chemokine receptor interactions are critical for the recruitment of bone marrow-derived progenitors. Once fibrocytes arrive in injured tissues, local factors induce their differentiation into fibroblasts/myofibroblasts. This review will summarize the experimental findings, supporting a role for the participation of bone marrow-derived cells in animal models of lung fibrosis, and potential implications for the pathogenesis of fibrotic lung diseases.
authors: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA.
authors: Bethany B
authors: BB
authors: Moore
authors: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA.
authors: Victor J
authors: VJ
authors: Thannickal
authors: Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan Medical School, Ann Arbor, MI 48109-0642, USA.
authors: Galen B
authors: GB
authors: Toews
keywords: Fibrosis; bone marrow; chemokines; fibroblasts; fibrocytes; lung