Increased circulating fibrocytes in asthma with chronic airflow obstruction.

RATIONALE A proportion of patients with asthma present with chronic airflow obstruction (CAO). We hypothesized that this effect may result from increased activity of circulating fibroblast-like progenitor cells (fibrocytes) that could home to the airway mucosal wall. OBJECTIVES To compare the proportion, proliferation, and differentiation of circulating fibrocytes from patients with asthma with CAO or no airflow obstruction (NOA) and control subjects. METHODS We investigated circulating fibrocytes in 11 patients with asthma with CAO and a rapid decline in FEV(1), 9 patients with asthma with NOA, and 10 nonasthmatic control subjects. Blood nonadherent non-T (NANT) cells were incubated with fetal calf serum or each patient's own serum and fibrocytes expressing CD34, CD45, and collagen I with alpha-smooth muscle actin were identified by flow cytometry. MEASUREMENTS AND MAIN RESULTS A higher percentage of circulating fibrocytes in NANT cells was found in patients with CAO when compared with patients with NOA and control subjects. In CAO, the slope of the yearly decline in FEV(1) correlated with circulating fibrocytes (r = -0.756, n = 11, P < 0.01). When NANT cells from patients with CAO were cultured in the patients' own sera, more fibrocytes were detected than when cultured in sera from patients with NOA or from normal subjects. An anti-transforming growth factor (TGF)-beta(1)-neutralizing antibody inhibited alpha-smooth muscle actin-positive fibrocyte transformation from NANT cells of patients with CAO. Serum TGF-beta(1) levels were higher in patients with CAO than in patients with NOA or in normal subjects. CONCLUSIONS Circulating fibrocytes are increased in patients with asthma with CAO and can be transformed by TGF-beta(1) to myofibroblasts. Fibrocytes may contribute to airway obstruction in asthma.

[1]  M. Burdick,et al.  Differentiation of Human Circulating Fibrocytes as Mediated by Transforming Growth Factor-β and Peroxisome Proliferator-activated Receptor γ* , 2007, Journal of Biological Chemistry.

[2]  M. Hew,et al.  Expression and activation of TGF-β isoforms in acute allergen-induced remodelling in asthma , 2007, Thorax.

[3]  P. Scott,et al.  Fibrocytes from burn patients regulate the activities of fibroblasts , 2007, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[4]  A. Malmström,et al.  Tissue fibrocytes in patients with mild asthma: A possible link to thickness of reticular basement membrane? , 2006, Respiratory research.

[5]  S. Peters,et al.  Airway remodeling contributes to the progressive loss of lung function in asthma: an overview. , 2005, The Journal of allergy and clinical immunology.

[6]  M. Stacey,et al.  Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow. , 2005, Experimental cell research.

[7]  T. Moore,et al.  CCR2-mediated recruitment of fibrocytes to the alveolar space after fibrotic injury. , 2005, The American journal of pathology.

[8]  S. Wenzel,et al.  Increased TGF-β2 in severe asthma with eosinophilia , 2005 .

[9]  M. Burdick,et al.  Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. , 2004, The Journal of clinical investigation.

[10]  Shawn Cowper,et al.  Circulating fibrocytes: collagen-secreting cells of the peripheral blood. , 2004, The international journal of biochemistry & cell biology.

[11]  Yu-Chun Hsu,et al.  Three-Dimensional Reconstruction of the Rabbit Atrioventricular Conduction Axis by Combining Histological, Desmin, and Connexin Mapping Data , 2004, Circulation.

[12]  M. Stacey,et al.  Identification of Circulating Fibrocytes as Precursors of Bronchial Myofibroblasts in Asthma1 , 2003, The Journal of Immunology.

[13]  C. Metz.  Fibrocytes: a unique cell population implicated in wound healing , 2003, Cellular and Molecular Life Sciences CMLS.

[14]  Y. Nakamura,et al.  Increased immunoreactivity of stromal cell-derived factor‐1 and angiogenesis in asthma , 2003, European Respiratory Journal.

[15]  S. Holgate,et al.  Airway remodeling in asthma: new insights. , 2003, The Journal of allergy and clinical immunology.

[16]  A. Bush,et al.  Early thickening of the reticular basement membrane in children with difficult asthma. , 2003, American journal of respiratory and critical care medicine.

[17]  K. Chung,et al.  Interleukin‐5 in growth and differentiation of blood eosinophil progenitors in asthma: effect of glucocorticoids , 2001, British journal of pharmacology.

[18]  R. Bucala,et al.  Fibrocytes induce an angiogenic phenotype in cultured endothelial cells and promote angiogenesis in vivo , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  Craig Murdoch,et al.  CXCR4: chemokine receptor extraordinaire , 2000, Immunological reviews.

[20]  A. Redington.  Fibrosis and airway remodelling. , 2000, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[21]  J Bousquet,et al.  Asthma. From bronchoconstriction to airways inflammation and remodeling. , 2000, American journal of respiratory and critical care medicine.

[22]  J. Bousquet,et al.  Structural consequences of airway inflammation in asthma. , 2000, The Journal of allergy and clinical immunology.

[23]  R. Homer,et al.  Airway remodeling in asthma. , 1999, The Journal of clinical investigation.

[24]  K. Chung,et al.  Increased progenitor cell proliferation in the peripheral blood of patients with bronchial asthma: the role of nitric oxide. , 1999, The Journal of allergy and clinical immunology.

[25]  S. Peters,et al.  Airway remodeling and persistent airway obstruction in asthma. , 1999, The Journal of allergy and clinical immunology.

[26]  R. Olivenstein,et al.  Enhanced proteoglycan deposition in the airway wall of atopic asthmatics. , 1999, American journal of respiratory and critical care medicine.

[27]  P. O'Byrne,et al.  Myofibroblast involvement in the allergen-induced late response in mild atopic asthma. , 1997, American journal of respiratory cell and molecular biology.

[28]  R. Bucala,et al.  Peripheral blood fibrocytes: novel fibroblast-like cells that present antigen and mediate tissue repair. , 1997, Biochemical Society transactions.

[29]  P. Howarth,et al.  Airway wall remodelling in asthma. , 1997, Thorax.

[30]  S. Carpi,et al.  Endothelin-1 induces increased fibronectin expression in human bronchial epithelial cells. , 1996, Biochemical and biophysical research communications.

[31]  B. Make,et al.  Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. American Thoracic Society. , 1995, American journal of respiratory and critical care medicine.

[32]  R. Bucala,et al.  Circulating Fibrocytes Define a New Leukocyte Subpopulation That Mediates Tissue Repair , 1994, Molecular medicine.

[33]  E. Yelin,et al.  Work disability among adults with asthma. , 1993, Chest.

[34]  D. Heinegård,et al.  Altered expression of small proteoglycans, collagen, and transforming growth factor-beta 1 in developing bleomycin-induced pulmonary fibrosis in rats. , 1993, The Journal of clinical investigation.

[35]  J. Bousquet,et al.  Asthma: a disease remodeling the airways , 1992, Allergy.