Title

Expression of S100A8 Correlates with Inflammatory Lung Disease in Congenic Mice Deficient of the Cystic Fibrosis Transmembrane Conductance Regulator

Authors

Sam Tirkos, University of Toronto
Susan Newbigging, University of Guelph
Van Nguyen, University of Toronto
Mary Keet, University of Western OntarioFollow
Cameron Ackerley, The Hospital for Sick Children, Toronto, ON
Geraldine Kent, The Hospital for Sick Children, Toronto, ON
Richard F. Rozmahel, University of Western Ontario

Document Type

Article

Publication Date

3-29-2006

Journal

Respiratory Research

Volume

7

Issue

51

Abstract

Background: Lung disease in cystic fibrosis (CF) patients is dominated by chronic inflammation with an early and inappropriate influx of neutrophils causing airway destruction. Congenic C57BL/6 CF mice develop lung inflammatory disease similar to that of patients. In contrast, lungs of congenic BALB/c CF mice remain unaffected. The basis of the neutrophil influx to the airways of CF patients and C57BL/6 mice, and its precipitating factor(s) (spontaneous or infection induced) remains unclear.

Methods: The lungs of 20-day old congenic C57BL/6 (before any overt signs of inflammation) and BALB/c CF mouse lines maintained in sterile environments were investigated for distinctions in the neutrophil chemokines S100A8 and S100A9 by quantitative RT-PCR and RNA in situ hybridization, that were then correlated to neutrophil numbers.

Results: The lungs of C57BL/6 CF mice had spontaneous and significant elevation of both neutrophil chemokines S100A8 and S100A9 and a corresponding increase in neutrophils, in the absence of detectable pathogens. In contrast, BALB/c CF mouse lungs maintained under identical conditions, had similar elevations of S100A9 expression and resident neutrophil numbers, but diverged in having normal levels of S100A8.

Conclusion: The results indicate early and spontaneous lung inflammation in CF mice, whose progression corresponds to increased expression of both S100A8 and S100A9, but not S100A9 alone. Moreover, since both C57BL/6 and BALB/c CF lungs were maintained under identical conditions and had similar elevations in S100A9 and neutrophils, the higher S100A8 expression in the former (or suppression in latter) is a result of secondary genetic influences rather than environment or differential infection.

Notes

Published in: Respiratory Research, 2006, 7:51. doi: 10.1186/1465-9921-7-51