Altered sputum granzyme B and granzyme B/proteinase inhibitor-9 in patients with non-eosinophilic asthma
Jodie L Simpson
Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Search for more papers by this authorPeter G Gibson
Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Search for more papers by this authorIan A Yang
School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
The Prince Charles Hospital, Brisbane, Queensland, Australia
Search for more papers by this authorJohn Upham
School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
Princess Alexandra Hospital, Brisbane, Queensland, Australia
Search for more papers by this authorAlan James
Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
Search for more papers by this authorPaul N Reynolds
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia
Joint Senior Authorship: Paul N Reynolds and Sandra Hodge contributed equally to this work.Search for more papers by this authorCorresponding Author
Sandra Hodge
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia
Joint Senior Authorship: Paul N Reynolds and Sandra Hodge contributed equally to this work.Correspondence: Sandra Hodge, Lung Research, Hanson Institute, Frome Road, Adelaide, SA 5001, Australia. Email: [email protected]Search for more papers by this authorAMAZES Study Research Group
Search for more papers by this authorJodie L Simpson
Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Search for more papers by this authorPeter G Gibson
Centre for Asthma and Respiratory Disease, The University of Newcastle, Newcastle, New South Wales, Australia
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Hunter Medical Research Institute, Newcastle, New South Wales, Australia
Search for more papers by this authorIan A Yang
School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
The Prince Charles Hospital, Brisbane, Queensland, Australia
Search for more papers by this authorJohn Upham
School of Medicine, The University of Queensland, Brisbane, Queensland, Australia
Princess Alexandra Hospital, Brisbane, Queensland, Australia
Search for more papers by this authorAlan James
Sir Charles Gairdner Hospital, Perth, Western Australia, Australia
Search for more papers by this authorPaul N Reynolds
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia
Joint Senior Authorship: Paul N Reynolds and Sandra Hodge contributed equally to this work.Search for more papers by this authorCorresponding Author
Sandra Hodge
Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
Lung Research Laboratory, Hanson Institute, Adelaide, South Australia, Australia
Joint Senior Authorship: Paul N Reynolds and Sandra Hodge contributed equally to this work.Correspondence: Sandra Hodge, Lung Research, Hanson Institute, Frome Road, Adelaide, SA 5001, Australia. Email: [email protected]Search for more papers by this authorAMAZES Study Research Group
Search for more papers by this authorAbstract
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.
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