G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages

Gordon R. Thomas, Elaine A. Costelloe, Dominic P. Lunn, Katryn J. Stacey, Steven J. Delaney, Robert Passey, Edwina C. McGlinn, Brendan J. McMorran, Azita Ahadizadeh, Carolyn L. Geczy, Brandon J. Wainwright, David A. Hume

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Abstract

The major cause of death in cystic fibrosis (CF) is chronic lung disease associated with persistent infection by the bacterium, Pseudomonas aeruginosa. S100A8, an S-100 calcium-binding protein with chemotactic activity, is constitutively expressed in the lungs and serum of CF patients. Levels of S100A8 mRNA were found to be three to four times higher in the lungs of mice carrying the G551D mutation in CF transmembrane conductance regulator compared with littermate controls. Intravenous injection of bacterial LPS induced S100A8 mRNA in the lung to a greater extent in G551D mice than in wild-type littermates. Localization of S100A8 mRNA and protein in the lung indicate that it is a marker for neutrophil accumulation. Bone marrow-derived macrophages from G551D mice were shown to also exhibit hypersensitivity to LPS, measured by induction of TNF-α. These results provide evidence that the pathology of CF relates to abnormal regulation of the immune system.

Original languageEnglish
Pages (from-to)3870-3877
Number of pages8
JournalJournal of Immunology
Volume164
Issue number7
DOIs
Publication statusPublished - 1 Apr 2000
Externally publishedYes

Cite this

Thomas, G. R., Costelloe, E. A., Lunn, D. P., Stacey, K. J., Delaney, S. J., Passey, R., ... Hume, D. A. (2000). G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages. Journal of Immunology, 164(7), 3870-3877. https://doi.org/10.4049/jimmunol.164.7.3870
Thomas, Gordon R. ; Costelloe, Elaine A. ; Lunn, Dominic P. ; Stacey, Katryn J. ; Delaney, Steven J. ; Passey, Robert ; McGlinn, Edwina C. ; McMorran, Brendan J. ; Ahadizadeh, Azita ; Geczy, Carolyn L. ; Wainwright, Brandon J. ; Hume, David A. / G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages. In: Journal of Immunology. 2000 ; Vol. 164, No. 7. pp. 3870-3877.
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abstract = "The major cause of death in cystic fibrosis (CF) is chronic lung disease associated with persistent infection by the bacterium, Pseudomonas aeruginosa. S100A8, an S-100 calcium-binding protein with chemotactic activity, is constitutively expressed in the lungs and serum of CF patients. Levels of S100A8 mRNA were found to be three to four times higher in the lungs of mice carrying the G551D mutation in CF transmembrane conductance regulator compared with littermate controls. Intravenous injection of bacterial LPS induced S100A8 mRNA in the lung to a greater extent in G551D mice than in wild-type littermates. Localization of S100A8 mRNA and protein in the lung indicate that it is a marker for neutrophil accumulation. Bone marrow-derived macrophages from G551D mice were shown to also exhibit hypersensitivity to LPS, measured by induction of TNF-α. These results provide evidence that the pathology of CF relates to abnormal regulation of the immune system.",
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Thomas, GR, Costelloe, EA, Lunn, DP, Stacey, KJ, Delaney, SJ, Passey, R, McGlinn, EC, McMorran, BJ, Ahadizadeh, A, Geczy, CL, Wainwright, BJ & Hume, DA 2000, 'G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages', Journal of Immunology, vol. 164, no. 7, pp. 3870-3877. https://doi.org/10.4049/jimmunol.164.7.3870

G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages. / Thomas, Gordon R.; Costelloe, Elaine A.; Lunn, Dominic P.; Stacey, Katryn J.; Delaney, Steven J.; Passey, Robert; McGlinn, Edwina C.; McMorran, Brendan J.; Ahadizadeh, Azita; Geczy, Carolyn L.; Wainwright, Brandon J.; Hume, David A.

In: Journal of Immunology, Vol. 164, No. 7, 01.04.2000, p. 3870-3877.

Research output: Contribution to journalArticleResearchpeer-review

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Thomas GR, Costelloe EA, Lunn DP, Stacey KJ, Delaney SJ, Passey R et al. G551D cystic fibrosis mice exhibit abnormal regulation of inflammation in lungs and macrophages. Journal of Immunology. 2000 Apr 1;164(7):3870-3877. https://doi.org/10.4049/jimmunol.164.7.3870