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Published ahead of print on June 26, 2008, doi:10.1164/rccm.200710-1557OC

Am. J. Respir. Crit. Care Med., Volume 178, Number 6, September 2008, 583-591

A more recent version of this article appeared on September 15, 2008
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Submitted on October 22, 2007
Accepted on June 26, 2008

Increased Circulating Fibrocytes in Asthma with Chronic Airflow Obstruction

Chun-Hua Wang1, Chien-Da Huang2, Horng-Chyuan Lin1, Kang-Yun Lee2, Shu-Min Lin3, Chien-Ying Liu2, Kuo-Hsiung Huang3, Yu-Shien Ko4, Kian Fan Chung5, and Han-Pin Kuo2*

1 Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Chinese Medicine, Chang Gung University, Taoyuan, Taiwan, 2 Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan; Department of Medicine, Chang Gung University, Taoyuan, Taiwan, 3 Department of Thoracic Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan, 4 First Cardiovascular Division, Chang Gung Memorial Hospital, Taipei, Taiwan, 5 National Heart and Lung Institute, Imperial College, London, United Kingdom

* To whom correspondence should be addressed. E-mail: q8828{at}ms11.hinet.net.

Rationale: A proportion of patients with asthma present with chronic airflow obstruction (CAO). We hypothesised that these effects 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 asthmatics with CAO or no airflow obstruction (NOA) and control subjects. Methods: We investigated circulating fibrocytes in 11 asthmatics with CAO and a rapid decline in FEV1, 9 asthmatics with NOA, and 10 non-asthmatic controls. Blood non-adherent non-T (NANT) cells were incubated with fetal calf serum (FCS) or patient's own sera and fibrocytes expressing CD34, CD45 and collagen 1 with {alpha}-smooth muscle actin ({alpha}-SMA) were identified by flow cytometry. Measurements and Main Results: A higher percentage of circulating fibrocytes in NANT cells was found in CAO when compared to NOA and controls. In CAO, the slope of the yearly decline in FEV1 correlated with circulating fibrocytes (r=-0.756, n=11, p<0.01). When NANT cells from CAO were cultured in the patient's own serum, more fibrocytes were detected than when cultured in sera from NOA or from normal subjects. An anti-TGF-{beta}1 neutralizing antibody inhibited {alpha}-SMA+ fibrocyte transformation from NANT cells of CAO patients. Serum TGF-{beta}1 levels were higher in CAO than in NOA or normal subjects. Conclusions: Circulating fibrocytes are increased in asthmatic patients with chronic airflow obstruction and can be transformed by TGF-{beta}1 to myofibroblasts. Fibrocytes may contribute to airway obstruction in asthma.


Key words: asthma,fibrocytes, myofibroblast,transforming growth factor-beta; airway remodeling







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