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Professor Tony Kettle

Tony Kettle

Principal Investigator, Centre for Free Radical Research
Research Professor

BSc(Hons) PhD(Otago) MSc(SFU) FRSNZ

Email tony.kettle@otago.ac.nz
Tel +64 3 364 0577

Research interests

For the past 25 years, we have probed the enzymology of myeloperoxidase (MPO). This haem protein gives pus and phlegm their characteristic green tinge. MPO produces chlorine bleach from hydrogen peroxide and common salt.

The knowledge from this work has helped us understand how white blood cells called neutrophils use MPO to kill bacteria. It has also revealed that chlorine bleach and free radicals contribute to inflammation.

We have shown that chlorine bleach promotes inflammatory tissue damage in cystic fibrosis, asthma, rheumatoid arthritis, and cardiovascular disease. In collaboration with AstraZeneca, we have also developed specific inhibitors of MPO that are potential anti-inflammatory drugs.

Current research topics


Cystic Fibrosis

Cycstic fibrosis and oxidative stress

Heart Disease

Plaque developing inside a blood vessel

Neutrophils

Bacteria killing by neutrophils

Radical Reactions

Radical Reactions

Myeloperoxidase

Mechanisms of inhibition of myeloperoxidase

Biomarkers

Biomarkers of hypochlorous acid

Public Health Lectures

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In the media

Professor Kettle was interviewed for Radio New Zealand's Our Changing World series in October 2014.

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Publications

Ashby, L. V., Dickerhof, N., Springer, R., Hampton, M. B., & Kettle, A. J. (2022, August). Bacterial resistance to oxidants in neutrophil phagosomes. Poster session presented at the Webster Centre for Infectious Diseases Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Dickerhof, N., Parker, H. A., Hampton, M. B., & Kettle, A. J. (2022, August). Gauging the exposure of bacteria to toxic oxidants inside neutrophil phagosomes. Poster session presented at the Webster Centre for Infectious Diseases Satellite Meeting: Queenstown Research Week, Queenstown, New Zealand.

Swaminathan, A., Frampton, C. M., Borichevsky, G. M., Kettle, A. J., & Gearry, R. B. (2022). Response to "Evaluating discriminative accuracy of biomarkers in relation to binary study outcomes: First validate, then celebrate?" Journal of Crohn's & Colitis. Advance online publication. doi: 10.1093/ecco-jcc/jjac126

Swaminathan, A., Borichevsky, G. M., Edwards, T. S., Hirschfeld, E., Mules, T. C., Frampton, C. M., Hampton, M. B., Kettle, A. J., & Gearry, R. B. (2022). Faecal myeloperoxidase as a biomarker of endoscopic activity in inflammatory bowel disease. Journal of Crohn's & Colitis. Advance online publication. doi: 10.1093/ecco-jcc/jjac098

Ashby, L. V., Springer, R., Loi, V. V., Antelmann, H., Hampton, M. B., Kettle, A. J., & Dickerhof, N. (2022). Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes. Journal of Leukocyte Biology. Advance online publication. doi: 10.1002/jlb.4hi1021-538rr

Vissers, M. C. M., Hampton, M. B., & Kettle, A. J. (Eds.). (2018). Hydrogen peroxide metabolism in health and disease. Boca Raton, FL: CRC Press, 456p.

Edited Book - Research

Garai, D., Pálinkás, Z., Balla, J., Kettle, A. J., & Nagy, P. (2019). Measurements for sulfide-mediated inhibition of myeloperoxidase activity. In J. Beltowski (Ed.), Vascular effects of hydrogen sulfide: Methods and protocols: Methods in molecular biology (Vol. 2007). (pp. 179-203). New York, NY: Humana Press. doi: 10.1007/978-1-4939-9528-8_14

Chapter in Book - Research

Forbes, L. V., & Kettle, A. J. (2018). Myeloperoxidase: Unleashing the power of hydrogen peroxide. In M. C. M. Vissers, M. B. Hampton & A. J. Kettle (Eds.), Hydrogen peroxide metabolism in health and disease. (pp. 281-304). Boca Raton, FL: CRC Press.

Chapter in Book - Research

Kettle, A. J., & Winterbourn, C. C. (2016). Myeloperoxidase: Structure and function of the green heme peroxidase of neutrophils. In E. Raven & B. Dunford (Eds.), Heme peroxidases. (pp. 272-308). Cambridge, UK: Royal Society of Chemistry. doi: 10.1039/9781782622628-00272

Chapter in Book - Research

Winterbourn, C. C., van Dalen, C. J., Hampton, M. B., & Kettle, A. J. (2000). Reactions of myeloperoxidase and production of hypochlorous acid in neutrophil phagosomes. In P. E. Petrides & W. M. Nauseef (Eds.), The Peroxidase Multigene Family of Enzymes. (pp. 58-67). Berlin: Springer.

Chapter in Book - Research

McPherson, K. G., Kettle, A. J., & Winterbourn, C. C. (1997). Mechanism of activation of NFKB by hydrogen peroxide in Jurkat JR cells. In L. Montagnier, R. Olivier & C. Pasquier (Eds.), Oxidative Stress and Redox Regulation: Cellular Signalling, Aids, Cancer and Other Diseases. (pp. 83-87). New York: Marcel Dekker.

Chapter in Book - Research

Kettle, A. J., & Winterbourn, C. C. (1996). Reaction mechanisms of myeloperoxidase. In C. Obinger, U. Burner, R. Ebermann, C. Penel & H. Greppin (Eds.), Plant Peroxidases: Biochemistry and Physiology. (pp. 134-139). Geneva: University of Geneva.

Chapter in Book - Research

Winterbourn, C., & Kettle, T. (2013). Centre for Free Radical Research. In P. Joyce, G. Nicholls, K. Thomas & T. Wilkinson (Eds.), The Christchurch experience: 40 years of research and teaching. (pp. 75-78). Christchurch, New Zealand: University of Otago.

Chapter in Book - Other

Ashby, L. V., Springer, R., Loi, V. V., Antelmann, H., Hampton, M. B., Kettle, A. J., & Dickerhof, N. (2022). Oxidation of bacillithiol during killing of Staphylococcus aureus USA300 inside neutrophil phagosomes. Journal of Leukocyte Biology. Advance online publication. doi: 10.1002/jlb.4hi1021-538rr

Journal - Research Article

Edwards, T. S., Dickerhof, N., Magon, N. J., Paton, L. N., Sly, P. D., & Kettle, A. J. (2022). Formation of calprotectin-derived peptides in the airways of children with cystic fibrosis. Journal of Immunology, 208, 979-990. doi: 10.4049/jimmunol.2001017

Journal - Research Article

Shearer, H. L., Kaldor, C. D., Hua, H., Kettle, A. J., Parker, H. A., & Hampton, M. B. (2022). Resistance of Streptococcus pneumoniae to hypothiocyanous acid generated by host peroxidases. Infection & Immunity. Advance online publication. doi: 10.1128/iai.00530-21

Journal - Research Article

Smyth, L. C. D., Murray, H. C., Hill, M., van Leeuwen, E., Highet, B., Magon, N. J., … Mathiesen, S. N., Mockett, B., … Clarkson, A. N., … Abraham, W. C., Hughes, S. M., … Kettle, A. J., … Hampton, M. B. (2022). Neutrophil-vascular interactions drive myeloperoxidase accumulation in the brain in Alzheimer's disease. Acta Neuropathologicca Communications, 10, 38. doi: 10.1186/s40478-022-01347-2

Journal - Research Article

Swaminathan, A., Borichevsky, G. M., Edwards, T. S., Hirschfeld, E., Mules, T. C., Frampton, C. M., Hampton, M. B., Kettle, A. J., & Gearry, R. B. (2022). Faecal myeloperoxidase as a biomarker of endoscopic activity in inflammatory bowel disease. Journal of Crohn's & Colitis. Advance online publication. doi: 10.1093/ecco-jcc/jjac098

Journal - Research Article

Parker, H. A., Dickerhof, N., Forrester, L., Ryburn, H., Smyth, L., Messens, J., Aung, H. L., Cook, G. M., Kettle, A. J., & Hampton, M. B. (2021). Mycobacterium smegmatis resists the bactericidal activity of hypochlorous acid produced in neutrophil phagosomes. Journal of Immunology, 206, 1901-1912. doi: 10.4049/jimmunol.2001084

Journal - Research Article

Bathish, B., Paumann-Page, M., Paton, L. N., Kettle, A. J., & Winterbourn, C. C. (2020). Peroxidasin mediates bromination of tyrosine residues in the extracellular matrix. Journal of Biological Chemistry, 295(36), 12697-12705. doi: 10.1074/jbc.RA120.014504

Journal - Research Article

Carr, A. C., Spencer, E., Hoskin, T. S., Rosengrave, P., Kettle, A. J., & Shaw, G. (2020). Circulating myeloperoxidase is elevated in septic shock and is associated with systemic organ failure and mortality in critically ill patients. Free Radical Biology & Medicine, 152, 462-468. doi: 10.1016/j.freeradbiomed.2019.11.004

Journal - Research Article

Dickerhof, N., Huang, J., Min, E., Michaëlsson, E., Lindstedt, E.-L., Pearson, J. F., Kettle, A. J., & Day, B. J. (2020). Myeloperoxidase inhibition decreases morbidity and oxidative stress in mice with cystic fibrosis-like lung inflammation. Free Radical Biology & Medicine, 152, 91-99. doi: 10.1016/j.freeradbiomed.2020.03.001

Journal - Research Article

Dickerhof, N., Paton, L., & Kettle, A. J. (2020). Oxidation of bacillithiol by myeloperoxidase-derived oxidants. Free Radical Biology & Medicine, 158, 74-83. doi: 10.1016/j.freeradbiomed.2020.06.009

Journal - Research Article

Schneider, M., Hannaway, R. F., Lamichhane, R., de la Harpe, S. M., Tyndall, J. D. A., Vernall, A. J., Kettle, A. J., & Ussher, J. E. (2020). Neutrophils suppress mucosal-associated invariant T cells in humans. European Journal of Immunology, 50, 643-655. doi: 10.1002/eji.201948394

Journal - Research Article

Cheng, D., Talib, J., Stanley, C. P., Rashid, I., Michaëlsson, E., Lindstedt, E.-L., … Kettle, A. J., … Stocker, R. (2019). Inhibition of MPO (myeloperoxidase) attenuates endothelial dysfunction in mouse models of vascular inflammation and atherosclerosis. Arteriosclerosis, Thrombosis, & Vascular Biology, 39, 1448-1457. doi: 10.1161/atvbaha.119.312725

Journal - Research Article

Dickerhof, N., Isles, V., Pattemore, P., Hampton, M. B., & Kettle, A. J. (2019). Exposure of Pseudomonas aeruginosa to bactericidal hypochlorous acid during neutrophil phagocytosis is compromised in cystic fibrosis. Journal of Biological Chemistry, 294(36), 13502-13514. doi: 10.1074/jbc.RA119.009934

Journal - Research Article

Filbey, K. J., Camberis, M., Chandler, J., Turner, R., Kettle, A. J., Eichenberger, R. M., … Le Gros, G. (2019). Intestinal helminth infection promotes IL-5- and CD4+ T cell-dependent immunity in the lung against migrating parasites. Mucosal Immunology, 12, 352-362. doi: 10.1038/s41385-018-0102-8

Journal - Research Article

Hoskin, T. S., Crowther, J. M., Cheung, J., Epton, M. J., Sly, P. D., Elder, P. A., … Kettle, A. J., & Dickerhof, N. (2019). Oxidative cross-linking of calprotectin occurs in vivo, altering its structure and susceptibility to proteolysis. Redox Biology, 24, 101202. doi: 10.1016/j.redox.2019.101202

Journal - Research Article

Albrett, A. M., Ashby, L. V., Dickerhof, N., Kettle, A. J., & Winterbourn, C. C. (2018). Heterogeneity of hypochlorous acid production in individual neutrophil phagosomes revealed by a rhodamine-based probe. Journal of Biological Chemistry, 293(40), 15715-15724. doi: 10.1074/jbc.RA118.004789

Journal - Research Article

Bathish, B., Turner, R., Paumann-Page, M., Kettle, A. J., & Winterbourn, C. C. (2018). Characterisation of peroxidasin activity in isolated extracellular matrix and direct detection of hypobromous acid formation. Archives of Biochemistry & Biophysics, 646, 120-127. doi: 10.1016/j.abb.2018.03.038

Journal - Research Article

Coker, M. S., Forbes, L. V., Plowman-Holmes, M., Murdoch, D. R., Winterbourn, C. C., & Kettle, A. J. (2018). Interactions of staphyloxanthin and enterobactin with myeloperoxidase and reactive chlorine species. Archives of Biochemistry & Biophysics, 646, 80-89. doi: 10.1016/j.abb.2018.03.039

Journal - Research Article

Das, A. B., Sadowska-Bartosz, I., Königstorfer, A., Kettle, A. J., & Winterbourn, C. C. (2018). Superoxide dismutase protects ribonucleotide reductase from inactivation in yeast. Free Radical Biology & Medicine, 116, 114-122. doi: 10.1016/j.freeradbiomed.2018.01.001

Journal - Research Article

Forbes, L. V., & Kettle, A. J. (2018). A multi-substrate assay for finding physiologically effective inhibitors of myeloperoxidase. Analytical Biochemistry, 544, 13-21. doi: 10.1016/j.ab.2017.12.022

Journal - Research Article

Khalilova, I. S., Dickerhof, N., Mocatta, T. J., Bhagra, C. J., McClean, D. R., Obinger, C., & Kettle, A. J. (2018). A myeloperoxidase precursor, pro-myeloperoxidase, is present in human plasma and elevated in cardiovascular disease patients. PLoS ONE, 13(3), e0192952. doi: 10.1371/journal.pone.0192952

Journal - Research Article

Rashid, I., Maghzal, G. J., Chen, Y.-C., Cheng, D., Talib, J., Newington, D., … Kettle, A. J., … Stocker, R. (2018). Myeloperoxidase is a potential molecular imaging and therapeutic target for the identification and stabilization of high-risk atherosclerotic plaque. European Heart Journal, 39(35), 3301-3310. doi: 10.1093/eurheartj/ehy419

Journal - Research Article

Turner, R., Brennan, S. O., Ashby, L. V., Dickerhof, N., Hamzah, M. R., Pearson, J. F., Stamp, L. K., & Kettle, A. J. (2018). Conjugation of urate-derived electrophiles to proteins during normal metabolism and inflammation. Journal of Biological Chemistry, 293(51), 19886-19898. doi: 10.1074/jbc.RA118.005237

Journal - Research Article

Dickerhof, N., Pearson, J. F., Hoskin, T. S., Berry, L. J., Turner, R., Sly, P. D., Kettle, A. J., on behalf of AREST CF. (2017). Oxidative stress in early cystic fibrosis lung disease is exacerbated by airway glutathione deficiency. Free Radical Biology & Medicine, 113, 236-243. doi: 10.1016/j.freeradbiomed.2017.09.028

Journal - Research Article

Dickerhof, N., Turner, R., Khalilova, I., Fantino, E., Sly, P. D., Kettle, A. J., on behalf of AREST CF. (2017). Oxidized glutathione and uric acid as biomarkers of early cystic fibrosis lung disease. Journal of Cystic Fibrosis, 16(2), 214-221. doi: 10.1016/j.jcf.2016.10.012

Journal - Research Article

Green, J. N., Chapman, A. L. P., Bishop, C. J., Winterbourn, C. C., & Kettle, A. J. (2017). Neutrophil granule proteins generate bactericidal ammonia chloramine on reaction with hydrogen peroxide. Free Radical Biology & Medicine, 113, 363-371. doi: 10.1016/j.freeradbiomed.2017.10.343

Journal - Research Article

Pullar, J. M., Carr, A. C., Bozonet, S. M., Rosengrave, P., Kettle, A. J., & Vissers, M. C. M. (2017). Elevated seminal plasma myeloperoxidase is associated with a decreased sperm concentration in young men. Andrology, 5(3), 431-438. doi: 10.1111/andr.12327

Journal - Research Article

Kato, Y., Oki, K., Suga, N., Ono, S., Ishisaka, A., Miura, Y., … Kettle, A. J. (2016). A novel quinone derived from 5-hydroxyindoleacetic acid reacts with protein: Possible participation of oxidation of serotonin and its metabolite in the development of atherosclerosis. Free Radical Biology & Medicine, 101, 500-510. doi: 10.1016/j.freeradbiomed.2016.11.023

Journal - Research Article

Terrill, J. R., Duong, M. N., Turner, R., Le Guiner, C., Boyatzis, A., Kettle, A. J., … Arthur, P. G. (2016). Levels of inflammation and oxidative stress, and a role for taurine in dystropathology of the Golden Retriever Muscular Dystrophy dog model for Duchenne Muscular Dystrophy. Redox Biology, 9, 276-286. doi: 10.1016/j.redox.2016.08.016

Journal - Research Article

Chandler, J. D., Min, E., Huang, J., McElroy, C. S., Dickerhof, N., Mocatta, T., … Kettle, A. J., … Day, B. J. (2015). Antiinflammatory and antimicrobial effects of thiocyanate in a cystic fibrosis mouse model. American Journal of Respiratory Cell & Molecular Biology, 53(2), 193-205. doi: 10.1165/rcmb.2014-0208OC

Journal - Research Article

Dickerhof, N., Schindler, L., Bernhagen, J., Kettle, A. J., & Hampton, M. B. (2015). Macrophage migration inhibitory factor (MIF) Is rendered enzymatically inactive by myeloperoxidase-derived oxidants but retains its immunomodulatory function. Free Radical Biology & Medicine, 89, 498-511. doi: 10.1016/j.freeradbiomed.2015.09.009

Journal - Research Article

Magon, N. J., Turner, R., Gearry, R. B., Hampton, M. B., Sly, P. D., & Kettle, A. J. (2015). Oxidation of calprotectin by hypochlorous acid prevents chelation of essential metal ions and allows bacterial growth: Relevance to infections in cystic fibrosis. Free Radical Biology & Medicine, 86, 133-144. doi: 10.1016/j.freeradbiomed.2015.05.022

Journal - Research Article

Odobasic, D., Muljadi, R. C. M., O'Sullivan, K. M., Kettle, A. J., Dickerhof, N., Summers, S. A., … Holdsworth, S. R. (2015). Suppression of autoimmunity and renal disease in pristane-induced lupus by myeloperoxidase. Arthritis & Rheumatology, 67(7), 1868-1880. doi: 10.1002/art.39109

Journal - Research Article

Patrício, E. S., Prado, F. M., da Silva, R. P., Carvalho, L. A. C., Prates, M. V. C., Dadamos, T., … Kettle, A. J., & Meotti, F. C. (2015). Chemical characterization of urate hydroperoxide, A pro-oxidant intermediate generated by urate oxidation in inflammatory and photoinduced processes. Chemical Research in Toxicology, 28(8), 1556-1566. doi: 10.1021/acs.chemrestox.5b00132

Journal - Research Article

Wilkie-Grantham, R. P., Magon, N. J., Harwood, D. T., Kettle, A. J., Vissers, M. C., Winterbourn, C. C., & Hampton, M. B. (2015). Myeloperoxidase-dependent lipid peroxidation promotes the oxidative modification of cytosolic proteins in phagocytic neutrophils. Journal of Biological Chemistry, 290(15), 9896-9905. doi: 10.1074/jbc.M114.613422

Journal - Research Article

Das, A. B., Nauser, T., Koppenol, W. H., Kettle, A. J., Winterbourn, C. C., & Nagy, P. (2014). Rapid reaction of superoxide with insulin-tyrosyl radicals to generate a hydroperoxide with subsequent glutathione addition. Free Radical Biology & Medicine, 70, 86-95. doi: 10.1016/j.freeradbiomed.2014.02.006

Journal - Research Article

Dickerhof, N., Magon, N. J., Tyndall, J. D. A., Kettle, A. J., & Hampton, M. B. (2014). Potent inhibition of macrophage migration inhibitory factor (MIF) by myeloperoxidase-dependant oxidation of epicatechins. Biochemical Journal, 462(2), 303-314. doi: 10.1042/BJ20140612

Journal - Research Article

Green, J. N., Kettle, A. J., & Winterbourn, C. C. (2014). Protein chlorination in neutrophil phagosomes and correlation with bacterial killing. Free Radical Biology & Medicine, 77, 49-56. doi: 10.1016/j.freeradbiomed.2014.08.013

Journal - Research Article

Kato, Y., Ono, S., Kitamoto, N., & Kettle, A. J. (2014). Covalent modification of cytoskeletal proteins in neuronal cells by tryptamine–4,5-dione. Redox Biology, 2, 983-990. doi: 10.1016/j.redox.2014.08.004

Journal - Research Article

Kettle, A. J., Albrett, A. M., Chapman, A. L., Dickerhof, N., Forbes, L. V., Khalilova, I., & Turner, R. (2014). Measuring chlorine bleach in biology and medicine. Biochimica et Biophysica Acta: General Subjects, 1840(2), 781-793. doi: 10.1016/j.bbagen.2013.07.004

Journal - Research Article

Kettle, A. J., Turner, R., Gangell, C. L., Harwood, D. T., Khalilova, I. S., Chapman, A. L., Winterbourn, C. C., … on behalf of AREST CF. (2014). Oxidation contributes to low glutathione in the airways of children with cystic fibrosis. European Respiratory Journal, 44, 122-129. doi: 10.1183/09031936.00170213

Journal - Research Article

Maghzal, G. J., Cergol, K. M., Shengule, S. R., Suarna, C., Newington, D., Kettle, A. J., … Stocker, R. (2014). Assessment of myeloperoxidase activity by the conversion of hydroethidine to 2-chloroethidium. Journal of Biological Chemistry, 289(9), 5580-5595. doi: 10.1074/jbc.M113.539486

Journal - Research Article

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