Altered sputum granzyme B and granzyme B/proteinase inhibitor-9 in patients with non-eosinophilic asthma

Simpson, Jodie L., Gibson, Peter G., Yang, Ian A., Upham, John, James, Alan, Reynolds, Paul N., Hodge, Sandra and AMAZES Study Research Group (2014) Altered sputum granzyme B and granzyme B/proteinase inhibitor-9 in patients with non-eosinophilic asthma. Respirology, 19 2: 280-287. doi:10.1111/resp.12213


Author Simpson, Jodie L.
Gibson, Peter G.
Yang, Ian A.
Upham, John
James, Alan
Reynolds, Paul N.
Hodge, Sandra
AMAZES Study Research Group
Total Author Count Override 8
Title Altered sputum granzyme B and granzyme B/proteinase inhibitor-9 in patients with non-eosinophilic asthma
Journal name Respirology   Check publisher's open access policy
ISSN 1323-7799
1440-1843
Publication date 2014-02
Year available 2013
Sub-type Article (original research)
DOI 10.1111/resp.12213
Open Access Status
Volume 19
Issue 2
Start page 280
End page 287
Total pages 8
Place of publication Richmond, VIC, Australia
Publisher Wiley-Blackwell
Collection year 2014
Language eng
Formatted abstract
Background and objective
The non-eosinophilic phenotype of asthma (NEA) is associated with chronic airway inflammation and airway neutrophilia. An accumulation of apoptotic airway epithelial cells, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, with the potential for inflammation of surrounding tissues. Apoptosis may occur via the T cell granzyme B pathway. The role of granzyme B in NEA is not known. The aim of this study was to investigate production of granzyme B and its inhibitor proteinase inhibitor (PI)-9 by T cells from induced sputum and compare expression between eosinophilic, NEA and healthy controls.

Methods
We investigated T cell intracellular granzyme B and its inhibitor, PI-9, in sputum from healthy control subjects (n = 10), and patients with NEA (n = 22) or eosinophilic asthma (EA) (n = 15) using flow cytometry.

Results
Granzyme B expression and the ratio of granzyme B to PI-9 positive cells were highest in those with NEA for both CD3+ and CD4+ T cells. The expression of granzyme B was not statistically different between patients with NEA and EA; however, the ratio of granzyme B to PI-9 positive cells for CD3+ T cells was significantly higher in those with NEA compared with EA.

Conclusions

Induced sputum provides a non-invasive tool for investigating T cell cytotoxic mediators in the various asthma subtypes. Granzyme B expression is increased in NEA and the contribution of granzyme B to chronic inflammation requires further study.
Keyword Asthma
Granzyme B
Lymphocyte
Non-eosinophilic asthma
Proteinase inhibitor-9
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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