David Greaves

Regulation of inflammatory responses in vivo

Inflammation is the response of vascularised tissues to injury, irritation and infection. The initial inflammatory response is localised to the site of injury, and is characterised by the rapid recruitment of plasma proteins and immune cells from the bloodstream. Acute inflammation typically lasts only a few days while chronic inflammation last for months or years, and is a defining feature of many important human diseases including rheumatoid arthritis, inflammatory bowel disease and coronary heart disease.

Macrophages with actin stained green and DNA in blue.

Inflamed human fallopian tube with neutrophils (dark blue nuclei) in a blood vessel.

The laboratory is studying the role played by a family of inflammatory mediators called chemokines in the recruitment and activation of monocytes and macrophages during chronic inflammation. We are interested in the role chemokines play in atherosclerosis - a disease process that occurs in arteries causing angina, heart attacks, strokes and peripheral arterial disease. In recent experiments, we have discovered that lipoprotein ApoA1 significantly down-regulates monocyte/macrophage responses to a wide range of inflammatory chemoattractants.

Work in the laboratory has also identified a new anti-inflammatory pathway in which peptides derived from the plasma protein chemerin potently reduce inflammatory cell recruitment in acute inflammation. Remarkably these peptides can also enhance the clearance of apoptotic cells by macrophages at sites of inflammation, and reduce the local production of chemokines and other inflammatory mediators.  These studies have identified a new avenue for the development of anti-inflammatory drugs.

Relevant Publications

Iqbal AJ, McNeill E, Kapellos TS, Regan-Komito D, Norman S, Burd S, Smart N, Machemer DE, Stylianou E, McShane H, Channon KM, Chawla A, Greaves DR
2014

Blood 124: e33-44.

White GE, McNeill E, Channon KM, Greaves DR
2014

Arterioscler Thromb Vasc Biol 34: 2554-62.

Cash JL, Christian AR, Greaves DR
2010

J Immunol 184: 5315-24.

david.greaves@path.ox.ac.uk

Research Areas