Nasal abnormalities in cystic fibrosis mice independent of infection and inflammation

Hilliard, Tom N., Zhu, Jie, Farley, Ray, Escudero-Garcia, Sara, Wainwright, Brandon J., Jeffery, Peter K., Griesenbach, Uta, Bush, Andrew, Davies, Jane C. and Alton, Eric W. F. W. (2008) Nasal abnormalities in cystic fibrosis mice independent of infection and inflammation. American Journal of Respiratory Cell and Molecular Biology, 39 1: 19-25. doi:10.1165/rcmb.2007-0284OC


Author Hilliard, Tom N.
Zhu, Jie
Farley, Ray
Escudero-Garcia, Sara
Wainwright, Brandon J.
Jeffery, Peter K.
Griesenbach, Uta
Bush, Andrew
Davies, Jane C.
Alton, Eric W. F. W.
Title Nasal abnormalities in cystic fibrosis mice independent of infection and inflammation
Journal name American Journal of Respiratory Cell and Molecular Biology   Check publisher's open access policy
ISSN 1044-1549
1535-4989
Publication date 2008-01-31
Year available 2008
Sub-type Article (original research)
DOI 10.1165/rcmb.2007-0284OC
Volume 39
Issue 1
Start page 19
End page 25
Total pages 7
Editor Kenneth B. Adler
Place of publication New York, NY, U.S.A.
Publisher American Thoracic Society
Language eng
Subject C1
920115 Respiratory System and Diseases (incl. Asthma)
0606 Physiology
1102 Cardiovascular Medicine and Haematology
Formatted abstract
It is not known whether the progressive airway changes in cystic fibrosis (CF) are all secondary to infection and inflammation. The CF mouse nose shares electrophysiologic and cellular properties with human CF airway epithelium. In the present work, we tested the hypothesis that structural abnormalities in the nasal mucosa of CF mice develop independent of infection and inflammation. We performed nasal lavage and subsequent serial coronal section through the nasal tissue of adult CF (mutations CftrTgHm1G551D and Cftrtm1Unc-TgN(FABPCFTR)) and wild-type mice raised under normal housing conditions. Nasal tissue was also obtained from Day 17 embryos and newborn pups. Detailed histologic examination of the respiratory and olfactory epithelium within the nasal cavity was performed. Bacterial culture, cell count, and macrophage inflammatory protein-2 (MIP-2) concentration were assessed in nasal lavage fluid. Significantly thickened respiratory epithelium and increased mucous cell density was found in adult CF mice of both mutations compared with wild-type animals. In contrast, the olfactory epithelium was thinner, with a decreased cell density. Areas of lymphoid aggregates were found in CF mice but not in non-CF mice. There were no differences in bacterial growth, cell count, or MIP-2 concentrations. No genotype differences were observed in the embryonic or newborn periods. There are significant histologic changes in the nasal mucosa of adult CF mice, not associated with increased lumenal inflammation or bacterial content, and which are not present perinatally. These may be novel therapeutic targets.
Keyword Mice
Cystic fibrosis
Pathology
Inflammation
Cystic fibrosis transmembrane conductance regulator
Q-Index Code C1
Q-Index Status Provisional Code

 
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