Identification of Circulating Fibrocytes as Precursors of Bronchial Myofibroblasts in Asthma
Open Access
- 1 July 2003
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 171 (1), 380-389
- https://doi.org/10.4049/jimmunol.171.1.380
Abstract
The mechanisms contributing to airway wall remodeling in asthma are under investigation to identify appropriate therapeutic targets. Bronchial myofibroblasts would represent an important target because they play a crucial role in the genesis of subepithelial fibrosis, a characteristic feature of the remodeling process, but their origin is poorly understood. We hypothesized that they originate from fibrocytes, circulating cells with the unique characteristic of expressing the hemopoietic stem cell Ag CD34 and collagen I. In this study we show that allergen exposure induces the accumulation of fibrocyte-like cells in the bronchial mucosa of patients with allergic asthma. These cells are CD34-positive; express collagen I and α-smooth muscle actin, a marker of myofibroblasts; and localize to areas of collagen deposition below the epithelium. By tracking labeled circulating fibrocytes in a mouse model of allergic asthma, we provide evidence that fibrocytes are indeed recruited into the bronchial tissue following allergen exposure and differentiate into myofibroblasts. We also show that human circulating fibrocytes acquire the myofibroblast phenotype under in vitro stimulation with fibrogenic cytokines that are produced in exaggerated quantities in asthmatic airways. These results indicate that circulating fibrocytes may function as myofibroblast precursors and may contribute to the genesis of subepithelial fibrosis in asthma.Keywords
This publication has 44 references indexed in Scilit:
- Fluorescent dyes for lymphocyte migration and proliferation studiesImmunology & Cell Biology, 1999
- Bronchial subepithelial fibrosis and expression of matrix metalloproteinase-9 in asthmatic airway inflammationJournal of Allergy and Clinical Immunology, 1998
- Endothelin-1 Induces Bronchial Myofibroblast DifferentiationPeptides, 1997
- The measurement of reticular basement membrane and submucosal collagen in the asthmatic airwayClinical & Experimental Allergy, 1997
- The measurement of reticular basement membrane and submucosal collagen in the asthmatic airwayClinical & Experimental Allergy, 1997
- Targeted expression of IL-11 in the murine airway causes lymphocytic inflammation, bronchial remodeling, and airways obstruction.JCI Insight, 1996
- Endothelin-1 Induces Increased Fibronectin Expression in Human Bronchial Epithelial CellsBiochemical and Biophysical Research Communications, 1996
- Constitutive expression of endothelin in bronchial epithelial cells of patients with symptomatic and asymptomatic asthma and modulation by histamine and interleukin-1Journal of Allergy and Clinical Immunology, 1995
- Levels of endothelin in the bronchoalveolar lavage fluid of patients with symptomatic asthma and reversible airflow obstructionJournal of Allergy and Clinical Immunology, 1991
- Selective Staining of Eosinophils and Their Immature Precursors in Tissue Sections and Autoradiographs with Congo RedStain Technology, 1981