Basal-like cells constitute the proliferating cell population in cystic fibrosis airways.
BACKGROUND
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.


OBJECTIVE
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 with 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.
Voynow
Judith A
JA
Department of Pediatrics, Duke University Medical Center, Durham, NC, USA. voyno001@mc.duke.edu
Fischer
Bernard M
BM
Roberts
Bruce C
BC
Proia
Alan D
AD
D000293:Adolescent; D000328:Adult; D001485:Basement Membrane / Q000648:ultrastructure; D001706:Biopsy; D001980:Bronchi / Q000737:chemistry / Q000648:ultrastructure*; D016022:Case-Control Studies; D002452:Cell Count; D049109:Cell Proliferation; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000648:ultrastructure*; D066246:ErbB Receptors / Q000032:analysis / Q000648:ultrastructure; D005260:Female; D020397:Goblet Cells / Q000648:ultrastructure; D006801:Humans; D006965:Hyperplasia; D019044:Image Cytometry; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D007633:Keratins / Q000032:analysis / Q000648:ultrastructure; D019394:Ki-67 Antigen / Q000032:analysis / Q000648:ultrastructure; D008297:Male; D008875:Middle Aged; D010784:Photomicrography; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000648:ultrastructure; D020545:Respiratory Mucosa / Q000737:chemistry / Q000648:ultrastructure*
D066246:ErbB Receptors; D007633:Keratins; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases