Investigating the collaborative role of endothelial sugars (glycosaminoglycans) and chemokines in leukocyte migration and inflammatory disease
|Starts:||11:00 1 Feb 2018|
|Ends:||12:00 1 Feb 2018|
|What is it:||Seminar|
|Organiser:||Faculty of Biology, Medicine and Health|
|Who is it for:||University staff|
“Despite recent advances, inflammatory disease remains a significant global health problem causing extensive pain and comorbidity in patients. Recruitment of inflammatory leukocytes to tissues is key in establishing and propagating inflammatory disease by producing local damage, leading to an inflammatory loop. Chemokines provide the key signals enabling circulating leukocytes to leave blood vessels and enter tissues. Despite extensive research chemokines (and their receptors) have not been successfully therapeutically targeted and new approaches are needed.
We have shown that chemokines cross-link heparan sulphate glycosaminoglycans (GAGs), key components of the endothelial glycocalyx, and modify the hydrated films they form via their ability to oligomerise. The glycocalyx is a thick, hydrated and adhesion resistant barrier that lines blood vessels, largely composed of proteoglycans. This structure is a critical, but understudied, regulator of leukocyte:endothelial interaction events and thus mediates leukocyte recruitment during inflammation and disease. Our findings suggest that chemokines may re-structure the glycocalyx, potentially increasing glycocalyx permeability and exposing endothelial surface adhesion molecules, enabling the molecular events underpinning inflammatory leukocyte migrations.
I propose that the interaction of chemokines with components of the glycocalyx (glycosaminoglycans) represents a novel and tractable therapeutic target. Advances in these areas will be critical to understanding, and targeting, chemokine function in a wide range of diseases from inflammatory pathologies to cancer.”
Organisation: University of Glasgow
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