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Intrinsic Biochemical and Functional Differences in Bronchial Epithelial Cells of Children with Asthma

Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth; School of Pediatrics and Child Health, The University of Western Australia, Nedlands; Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia; James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, and Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, Canada

Correspondence and requests for reprints should be addressed to Anthony Kicic, Ph.D., Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, 6001, Western Australia, Australia. E-mail: anthonyk{at}ichr.uwa.edu.au

Rationale: Convincing evidence of epithelial damage and aberrant repair exists in adult asthmatic airways, even in the absence of inflammation. However, comparable studies in children have been limited by access and availability of clinical samples.

Objectives: To determine whether bronchial epithelial cells from children with asthma are inherently distinct from those obtained from children without asthma.

Methods: Epithelial cells were obtained by nonbronchoscopic bronchial brushing of children with mild asthma (n = 7), atopic children without asthma (n = 9), and healthy children (n = 12). Cells were subject to morphologic, biochemical, molecular, and functional assessment. Responses were also compared with commercially available epithelial cultures and the transformed cell line 16HBE140.

Results: All epithelial cells exhibited a "cobblestone" morphology, which was maintained throughout culture and repeated passage. Expression of cytokeratin 19 varied, with disease phenotype being greatest in healthy nonatopics and lowest in asthmatics. In contrast, expression of cytokeratin 5/14 was greatest in asthmatic samples and least in healthy nonatopic samples. Asthmatic epithelial cells also spontaneously produced significantly greater amounts of interleukin (IL)-6, prostaglandin E₂, and epidermal growth factor, and equivalent amounts of IL-1 and soluble intracellular adhesion molecule-1, but significantly lower amounts of transforming growth factor 1. This profile was maintained through successive passages. Asthmatic epithelial cells also exhibited greater rates of proliferation than nonasthmatic cells.

Conclusions: This study has shown that epithelial cells from children with mild asthma are intrinsically different both biochemically and functionally compared with epithelial cells from children without asthma. Importantly, these differences are maintained over successive passages, suggesting that they are not dependent on an in vivo environment.

Key Words: airway • asthma • bronchial epithelium • cell • nonbronchoscopic brushing

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The airway epithelium plays a central role in the pathogenesis of asthma. However, these data have almost exclusively been generated from studies using adults, whereas it is likely that dysregulated epithelial repair originates in childhood asthma and is a critical determinant of disease progression into adulthood. What This Study Adds to the Field The results obtained provide strong evidence that there are marked inherent differences between healthy and asthmatic bronchial epithelium. In particular, the cytokeratin profiles, the augmented release of antiinflammatory mediators, and the markedly diminished production of TGF-1 support the argument that asthmatic epithelial cells function abnormally even in the absence of inflammation.

 

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