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Published ahead of print on July 14, 2005, doi:10.1164/rccm.200410-1398OC

Am. J. Respir. Crit. Care Med., Volume 172, Number 8, October 2005, 1013-1018

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Submitted on October 21, 2004
Accepted on July 14, 2005

Basal-Like Cells Constitute the Proliferating Cell Population in Cystic Fibrosis Airways

Judith A Voynow1*, Bernard M Fischer1, Bruce C Roberts2, and Alan D Proia2

1 Department of Pediatrics, Duke University Medical Center, Durham, NC, USA, 2 Department of Pathology, Duke University Medical Center, Durham, NC, USA

* To whom correspondence should be addressed. E-mail: voyno001{at}mc.duke.edu.

Rationale: Cystic fibrosis airways are recurrently exposed to noxious stimuli leading to epithelial injury. Previous reports suggest that cystic fibrosis airway epithelia may respond to injury by increasing proliferation. Objectives: We sought to determine the characteristics of the proliferating cell population in cystic fibrosis airways. Methods: Six cystic fibrosis and six normal lung sections from lung transplant recipients or lung surgery were obtained from the Duke Hospital Pathology archives. Sections containing bronchi were evaluated for epithelial cell proliferation using immunohistochemistry for a nuclear proliferation antigen, Ki-67, and image analysis; immunohistochemistry for basal cells using a cytokeratin 5/14 antibody; and immunohistochemistry for the epidermal growth factor receptor and ErbB2, two receptor tyrosine kinases implicated in epithelial proliferation and differentiation. Results: Overall, cystic fibrosis sections had a greater proliferation index than control sections with 25.1± 2.1% positively-staining nuclei/total nuclei compared to control sections, 4.6 ± 0.9%(p=0.002). In cystic fibrosis sections only, there were areas of hyperplastic cuboidal cells adjacent to normal pseudostratified columnar epithelial sections; in these areas of epithelial hyperplasia, there was uniform Ki-67 staining, indicating a zone of proliferating cells. The proliferating cell population also expressed the basal cell cytokeratins 5/14 and epidermal growth factor receptor. Expression of ErbB2 was diminished in the proliferating cells. Conclusions: Our results suggest that basal-like cells, expressing the epidermal growth factor receptor, constitute the proliferating cell population in cystic fibrosis airways.
Key words: EGFR, ErbB2, Ki-67, Epithelial repair




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