JCSMR School Seminar Series: B cells, autoantibodies and M2 macrophages are crucial mediators of vessel remodelling in hypertension

Associate Professor Grant Drummond, Department of Pharmacology, Monash University, Clayton, VIC.

In 1970, Professor Austin Doyle published the intriguing finding that essential hypertension in humans is associated with elevated serum levels of immunoglobulin G (IgG); an observation that has since been confirmed by numerous groups. However, despite the passage of almost 50 years, it remains to be determined whether IgG antibodies are causative agents in hypertension or merely secondary consequences of the tissue damage associated with the condition. Our recent work has shown that experimental hypertension in mice is similarly associated with elevated serum levels of IgG. Moreover, these autoantibodies accumulate in the vascular adventitia and promote the polarization of macrophages towards an M2-like phenotype characterized by an enhanced capacity to produce the pro-fibrotic cytokine transforming growth factor-beta. Importantly, mice that are deficient in B cells (i.e. the antibody-producing cells of the mammalian immune system), either due to genetic modifications or as a result of treatment with a B cell-depleting drug, do not display such increases in IgG and are profoundly protected from vascular remodelling and elevations in blood pressure following treatment with hypertensive agents such as angiotensin II. These findings add to a growing body of literature that is redefining hypertension as an autoimmune disorder. This is significant as it opens up possibilities for new treatment strategies for hypertension akin to those used already for classical autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and gout.

Grant Drummond is a NHMRC Senior Research Fellow and co-leader (with A/Prof Chris Sobey) of the Vascular Biology & Immunopharmacology Group in the Department of Pharmacology, Monash University. Over the past decade, Grant Drummond has built up a reputation as a leading vascular pharmacologist and biologist in Australia and internationally, with expertise in mechanisms and consequences of elevated reactive oxygen species (ROS) production and oxidative stress in cardiovascular disease. His work has provided insights into the roles of NADPH oxidase-derived ROS as novel signalling molecules under normal physiological conditions, and as mediators of oxidative damage in vascular disease states such as atherosclerosis, hypertension and stroke. More recently, Grant's work has begun unraveling the roles of the innate and adaptive immune systems in the pathogenesis of renal and vascular disease in hypertension.

Grant Drummond received his PhD from the Department of Pharmacology, University of Melbourne in 1998 and then completed 2 years of postdoctoral training at Emory University (Atlanta, USA) under Prof David Harrison. Grant returned to Australia in 2000 on a Peter Doherty Postdoctoral fellowship and spent 4 years working at the Howard Florey Institute with Prof Greg Dusting. He moved to Monash University in 2004 on a Monash Category I Fellowship and since this time has grown his research team such that it now comprises 7 postdocs, 2 research assistants, 7 postgraduate students and 4 Honours students.

Date & time

12–1pm 3 July 2015

Location

The Finkel Lecture Theatre, The John Curtin School of Medical Research, Building 131, Garran Road, ANU

Contacts

 Emma Dowling
 02 6125 2528

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