Increased circulating fibrocytes in asthma with chronic airflow obstruction.
BACKGROUND
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.


OBJECTIVE
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.


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.
Wang
Chun-Hua
CH
Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road, Taipei, Taiwan.
Huang
Chien-Da
CD
Lin
Horng-Chyuan
HC
Lee
Kang-Yun
KY
Lin
Shu-Min
SM
Liu
Chien-Ying
CY
Huang
Kuo-Hsiung
KH
Ko
Yu-Shien
YS
Chung
Kian Fan
KF
Kuo
Han-Pin
HP
D000199:Actins / Q000097:blood; D000402:Airway Obstruction / Q000150:complications; D018952:Antigens, CD34 / Q000097:blood; D001249:Asthma / Q000097:blood* / Q000150:complications; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005541:Forced Expiratory Volume; D006801:Humans; D018793:Interleukin-13 / Q000097:blood; D017493:Leukocyte Common Antigens / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D054400:Receptors, CCR7 / Q000097:blood; D019718:Receptors, CXCR4 / Q000097:blood; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000097:blood
C541116:ACTA2 protein, human; D000199:Actins; D018952:Antigens, CD34; C515370:CCR7 protein, human; C527276:CXCR4 protein, human; D018793:Interleukin-13; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D053773:Transforming Growth Factor beta1; D017493:Leukocyte Common Antigens