Research

Expression of S100A8 correlates with inflammatory lung disease in congenic mice deficient of the cystic fibrosis transmembrane conductance regulator

Sam Tirkos¹ , Susan Newbigging² , Van Nguyen¹ , Mary Keet^3,4 , Cameron Ackerley⁵ , Geraldine Kent⁵ and Richard F Rozmahel^1,3,4

¹Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada

²Department of Pathobiology, University of Guelph and Ontario Veterinary College, Guelph, Ontario, Canada

³University of Western Ontario, London, Ontario, Canada

⁴Lawson Health Research Institute, London, Ontario, Canada

⁵The Hospital for Sick Children, Toronto, ON, Canada

author email corresponding author email

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

Published:	29 March 2006

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.