Final published version
Licence: CC BY-NC-ND: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
Research output: Working paper › Preprint
Research output: Working paper › Preprint
}
TY - UNPB
T1 - Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during inflammation
AU - Priestley, Megan
AU - Hains, Anna
AU - Mulholland, Iashia
AU - Spijkers-Shaw, Sam
AU - Zubkova, Olga
AU - Dyer, Douglas
AU - Saunders, Amy
PY - 2024/6/5
Y1 - 2024/6/5
N2 - The glycocalyx is a proteoglycan-rich layer present on the surface of all mammalian cells that is particularly prevalent on endothelial cells lining the vasculature. It has been hypothesized that the glycocalyx mediates leukocyte migration by masking adhesion molecules and reducing leukocyte adhesion to the endothelium. Leukocyte recruitment is a key driver of inflammatory diseases, including the chronic skin disease, psoriasis. Here, we show that leukocytes express heparan sulfate, an important glycocalyx component, on their cell surface which is lost in response to psoriasis-like skin inflammation, whilst endothelial heparan sulfate expression is not affected. Treatment with a heparan sulfate mimetic during psoriasis-like skin inflammation protected heparan sulfate from cleavage by heparanase and resulted in reduced leukocyte accumulation in skin, yet unexpectedly, led to increased clinical signs of inflammation due to reduced Treg numbers. These findings reshape our understanding of immune cell recruitment by revealing the presence and function of a heparan sulfate glycocalyx on immune cells and highlight the complex effects of heparanase inhibitors on the immune response in this context.
AB - The glycocalyx is a proteoglycan-rich layer present on the surface of all mammalian cells that is particularly prevalent on endothelial cells lining the vasculature. It has been hypothesized that the glycocalyx mediates leukocyte migration by masking adhesion molecules and reducing leukocyte adhesion to the endothelium. Leukocyte recruitment is a key driver of inflammatory diseases, including the chronic skin disease, psoriasis. Here, we show that leukocytes express heparan sulfate, an important glycocalyx component, on their cell surface which is lost in response to psoriasis-like skin inflammation, whilst endothelial heparan sulfate expression is not affected. Treatment with a heparan sulfate mimetic during psoriasis-like skin inflammation protected heparan sulfate from cleavage by heparanase and resulted in reduced leukocyte accumulation in skin, yet unexpectedly, led to increased clinical signs of inflammation due to reduced Treg numbers. These findings reshape our understanding of immune cell recruitment by revealing the presence and function of a heparan sulfate glycocalyx on immune cells and highlight the complex effects of heparanase inhibitors on the immune response in this context.
U2 - 10.1101/2024.05.21.595098
DO - 10.1101/2024.05.21.595098
M3 - Preprint
BT - Leukocytes have a heparan sulfate glycocalyx that regulates recruitment during inflammation
PB - bioRxiv
ER -