Abstract
Leukocyte recruitment is a highly controlled cascade of interactions between proteins expressed by the endothelium and circulating leukocytes. The involvement of glycans and glycan-binding proteins in the leukocyte recruitment cascade has been well-characterised. However, our understanding of these interactions and their regulation has expanded substantially in recent years to include novel lectins and regulatory pathways. In this review, we discuss the role of glycans and glycan-binding proteins, mediating the interactions between endothelium and leukocytes both directly and indirectly. We also highlight recent findings of key enzymes involved in glycosylation which affect leukocyte recruitment. Finally, we investigate the potential of glycans and glycan binding proteins as therapeutic targets to modulate leukocyte recruitment and transmigration in inflammation.
Highlights
Glycosylation is a post-translational modification whereby carbohydrates are added to proteins or lipids to expand their functional profile
Crucial in glycosylation of ligands for P-selectin Knock down impedes leukocyte rolling, adhesion and transmigration Drosophila analogue of mammalian ppGalNT, alternative splicing alters substrate and peptide preference Necessary for fucosylation of P-selectin glycoprotein ligand (PSGL)-1 Knock downs decrease interaction with selectins in vitro and in vivo under flow Expression of Fut VII increased in activated T-cells so they can bind to selectins
Other in vitro studies targeting high mannose glycans with specific antibodies or lectins have successfully decreased monocyte adhesion further highlighting the therapeutic potential of targeting these glycan structures (Scott et al, 2012), these effects need to be validated in vivo
Summary
Glycosylation is a post-translational modification whereby carbohydrates are added to proteins or lipids to expand their functional profile. The roles of glycan-binding proteins such as selectins and glycosylated proteins including ICAM-1 in leukocyte recruitment and transmigration have been well-documented.
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