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“Caught in the act” – imaging white blood cells while they cause inflammatory injury

Professor Michael Hickey says leukocytes, or white blood cells, are both the good and bad guys of our immune system. While these cells are critical to our ability to fight infections and heal our tissues after injury, they are also responsible for some of the most debilitating inflammatory diseases, including rheumatoid arthritis, asthma, multiple sclerosis and inflammatory kidney disease. Michael’s laboratory investigates the behaviour of leukocytes in inflamed tissues and the blood vessels that supply them, using highly advanced microscopes to visualise white blood cells in tissues. The overall approach of the laboratory stems from the idea that only by directly visualising white blood cells in action can we aim to understand how they contribute to inflammatory diseases, and thereby identify new ways to tackle these conditions.

Leukocytes circulate in the blood vessels and migrate into tissues when they detect signs of infection or tissue damage. Inflammatory diseases occur when this response is excessive or inappropriately targeted. Michael’s research examines the process whereby the cells stick to blood vessel walls in order to leave the bloodstream and enter the inflammatory site.

'We investigate the dynamic process of how white blood cells move out of blood vessels' Michael says. 'It sounds simple but it's very diverse because the mechanisms of this process can be different in different organs and for different types of white blood cells. The strategy we use in my lab is to directly visualise these cells in specific tissues during inflammatory responses, with the aim of identifying the molecules involved in leukocyte accumulation in tissues,' he says.

While inappropriate inflammation can affect every tissue in the body, the main focus of Michael's current research is white blood cell-mediated inflammatory injury of the kidney, a major cause of kidney failure.

'The part of the kidney that filters the blood - the glomerulus - can be a target of various life-threatening inflammatory diseases,' Michael says. ‘We're one of the few labs in the world using microscopy to look specifically at this part of the kidney. We are using this approach to investigate the mechanisms whereby white blood cells are attracted to the glomerulus and to understand their behaviour once they get there. We've discovered some unique aspects whereby white blood cells injure this component of the kidney.

'We are also examining inflammatory disease of the skin,' he says. 'We've been studying a very rare kind of white blood cell – the regulatory T cell - that dampens down skin inflammation, examining the process whereby these cells get into the skin and identifying new processes whereby they control inflammation.'

The ultimate aim of this work is to develop a detailed molecular understanding of the mechanisms whereby leukocytes cause or alternatively control injury in inflamed tissues.

Professor Hickey's research has been supported by funding from the National Health & Medical Research Council, National Institutes of Health (US), the Heart Foundation of Australia, ANZ Trustees and the Rebecca L Cooper Foundation.

 

 

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Projects 2001 2022

Research Output 1990 2018

Activation of the sympathetic nervous system modulates neutrophil function

Nicholls, A. J., Wen, S. W., Hall, P., Hickey, M. J. & Wong, C. H. Y., 1 Feb 2018, In : Journal of leukocyte biology. 103, 2, p. 295-309 15 p.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

C5a receptor 1 promotes autoimmunity, neutrophil dysfunction and injury in experimental anti-myeloperoxidase glomerulonephritis

Dick, J., Gan, P. Y., Ford, S. L., Odobasic, D., Alikhan, M. A., Loosen, S. H., Hall, P., Westhorpe, C. L., Li, A., Ooi, J. D., Woodruff, T. M., Mackay, C. R., Kitching, A. R., Hickey, M. J. & Holdsworth, S. R., 1 Mar 2018, In : Kidney International. 93, 3, p. 615-625 11 p.

Research output: Contribution to journalArticleResearchpeer-review

CD39 and CD73 activity are protective in a mouse model of antiphospholipid antibody-induced miscarriages

Samudra, A. N., Dwyer, K. M., Selan, C., Freddi, S., Murray-Segal, L., Nikpour, M., Hickey, M. J., Peter, K., Robson, S. C., Sashindranath, M., Cowan, P. J. & Nandurkar, H. H., Mar 2018, In : Journal of Autoimmunity. 88, p. 131-138 8 p.

Research output: Contribution to journalArticleResearchpeer-review

Effector CD4+ T cells recognize intravascular antigen presented by patrolling monocytes

Westhorpe, C. L. V., Ursula Norman, M., Hall, P., Snelgrove, S. L., Finsterbusch, M., Li, A., Lo, C., Tan, Z. H., Li, S., Nilsson, S. K., Kitching, A. R. & Hickey, M. J., 1 Dec 2018, In : Nature Communications. 9, 1, 14 p., 747.

Research output: Contribution to journalArticleResearchpeer-review

Open Access
File

Glucose Homeostasis Is Important for Immune Cell Viability during Candida Challenge and Host Survival of Systemic Fungal Infection

Tucey, T. M., Verma, J., Harrison, P. F., Snelgrove, S. L., Lo, T. L., Scherer, A. K., Barugahare, A. A., Powell, D. R., Wheeler, R. T., Hickey, M. J., Beilharz, T. H., Naderer, T. & Traven, A., 1 May 2018, In : Cell Metabolism. 27, 5, p. 988-1006.e7 27 p.

Research output: Contribution to journalArticleResearchpeer-review