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

• Published in: American journal of respiratory and critical care medicine Vol. 172; no. 8; pp. 1013 - 1018
• Main Authors: Voynow, Judith A, Fischer, Bernard M, Roberts, Bruce C, Proia, Alan D
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 15.10.2005; American Lung Association; American Thoracic Society
• Subjects: Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antibodies; Antigens; Arms control & disarmament; Basement Membrane - ultrastructure; Biological and medical sciences; Biopsy; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow, stem cells transplantation. Graft versus host reaction; Bronchi - chemistry; Bronchi - ultrastructure; Case-Control Studies; Cell Count; Cell cycle; Cell Proliferation; Child, Preschool; Cystic fibrosis; Cystic Fibrosis - ultrastructure; Epidermal growth factor; Female; Goblet Cells - ultrastructure; Histology; Humans; Hyperplasia; Image Cytometry; Immunohistochemistry - methods; Infant; Intensive care medicine; Keratins - analysis; Keratins - ultrastructure; Ki-67 Antigen - analysis; Ki-67 Antigen - ultrastructure; Lung transplants; Male; Medical sciences; Middle Aged; Photomicrography; Receptor, Epidermal Growth Factor - analysis; Receptor, Epidermal Growth Factor - ultrastructure; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - ultrastructure; Respiratory Mucosa - chemistry; Respiratory Mucosa - ultrastructure; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Intensive care; Respiratory disease; Digestive diseases; Metabolic diseases; Cystic fibrosis; Resuscitation; Genetic disease; Pancreatic disease
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200410-1398OC

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. We sought to determine the characteristics of the proliferating cell population in cystic fibrosis airways. 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. 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. Our results suggest that basal-like cells, expressing the epidermal growth factor receptor, constitute the proliferating cell population in cystic fibrosis airways.