Nasal Abnormalities in Cystic Fibrosis Mice Independent of Infection and Inflammation
| Autor: | Peter K. Jeffery, Brandon J. Wainwright, Andrew Bush, Tom Hilliard, Sara Escudero-Garcia, Eric W.F.W. Alton, Uta Griesenbach, Ray Farley, Jie Zhu, Jane C. Davies |
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| Rok vydání: | 2008 |
| Předmět: |
Pulmonary and Respiratory Medicine
Nasal cavity Pathology medicine.medical_specialty Cystic Fibrosis Genotype Clinical Biochemistry Cystic Fibrosis Transmembrane Conductance Regulator Mice Transgenic Mucous membrane of nose Respiratory Mucosa Nose Infections Polymorphism Single Nucleotide Cystic fibrosis Mice Olfactory Mucosa otorhinolaryngologic diseases medicine Animals Humans Respiratory system Molecular Biology Inflammation business.industry Homozygote Cell Biology respiratory system medicine.disease Mice Mutant Strains Disease Models Animal medicine.anatomical_structure Immunology Nasal Lavage Respiratory epithelium Nasal Lavage Fluid business Olfactory epithelium |
| Zdroj: | American Journal of Respiratory Cell and Molecular Biology. 39:19-25 |
| ISSN: | 1535-4989 1044-1549 |
| DOI: | 10.1165/rcmb.2007-0284oc |
| Popis: | 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 Cftr(TgHm1G551D) and Cftr(tm1Unc)-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. |
| Databáze: | OpenAIRE |
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