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Published ahead of print on August 14, 2006, doi:10.1164/rccm.200603-392OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 10, November 2006, 1110-1118

A more recent version of this article appeared on November 15, 2006
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Submitted on March 17, 2006
Accepted on August 14, 2006

Intrinsic Biochemical and Functional Differences in Bronchial Epithelial Cells of Asthmatic Children

Anthony Kicic1*, Erika N Sutanto2, Paul T Stevens3, Darryl A Knight4, and Stephen M Stick1

1 Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; School of Pediatrics and Child Health, The University of Western Australia, Nedlands, Western Australia, Australia; Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia, 2 Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia, Australia; Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia, 3 School of Pediatrics and Child Health, The University of Western Australia, Nedlands, Western Australia, Australia; Telethon Institute for Child Health Research, Subiaco, Western Australia, Australia, 4 St. Paul's Hospital, James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, Vancouver, British Columbia, Canada; Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada

* To whom correspondence should be addressed. 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 asthmatic children are inherently distinct from those obtained from non-asthmatic children. Methods: Epithelial cells were obtained by non-bronchoscopic bronchial brushing of mild asthmatic (7), atopic non-asthmatic (9) and healthy children (12). Cells were subject to morphological, biochemical, molecular and functional assessment. Responses were also compared to commercially available epithelial cultures and the transformed cell line 16HBE140. Results: All epithelial cells exhibited a "cobblestone" morphology that was maintained throughout culture and repeated passage. Expression of cytokeratin-19 varied with disease phenotype being greatest in healthy non-atopics and lowest in asthmatics. In contrast, expression of cytokeratin 5/14 was greatest in asthmatics and least in healthy non-atopics samples. Asthmatic epithelial cells also spontaneous produced significantly greater amounts of IL-6, PGE2 and EGF, equivalent amounts of IL-1{beta}, sICAM-1, but significantly lower amounts of TGF{beta}-1. This profile was maintained through successive passage. Asthmatic epithelial cells also exhibited greater rates of proliferation than non-asthmatic cells. Conclusions: This study has shown that epithelial cells from mildly asthmatic children are intrinsically different both biochemically and functionally to epithelial cells from non-asthmatics. Importantly, these differences are maintained over successive passage, suggesting that they are not dependent on an in vivo environment.
Key words: Asthma, bronchial epithelium, non-bronchoscopic brushing, airway, cell




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