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Increased Circulating Fibrocytes in Asthma with Chronic Airflow Obstruction

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

Correspondence and requests for reprints should be addressed to Han-Pin Kuo, M.D., Ph.D., Department of Thoracic Medicine, Chang Gung Memorial Hospital, 199 Tun-Hwa North Road, Taipei, Taiwan. E-mail: q8828{at}ms11.hinet.net

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 FEV₁, 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 -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 FEV₁ 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)-β₁–neutralizing antibody inhibited -smooth muscle actin–positive fibrocyte transformation from NANT cells of patients with CAO. Serum TGF-β₁ 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-β₁ to myofibroblasts. Fibrocytes may contribute to airway obstruction in asthma.

Key Words: asthma • fibrocytes • myofibroblasts • transforming growth factor-β • airway remodeling

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Blood-borne fibrocytes characterized by expression of collagen I and CD45 and/or CD34 have been identified in asthma and are increased in the airways of patients with asthma after allergen challenge. What This Study Adds to the Field Circulating fibrocytes in the nonadherent non–T-cell fraction of peripheral blood mononuclear cells are increased in patients with asthma presenting with airflow obstruction and are correlated with the yearly decline in lung function; they can be transformed by TGF-β1 into myofibroblasts.

 

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