Vascular Endothelial Galectins in Leukocyte Trafficking

Abstract

Leukocyte recruitment to the site of injury is a crucial event in the regulation of an inflammatory response. Tight regulation of interactions between the endothelium and circulating leukocytes is necessary to ensure a protective response to injury does not result in inflammatory disease. Rising interest in the broad immunoregulatory roles displayed by members of the glycan-binding galectin family suggests that these proteins could be an attractive target for therapeutic intervention, since their expression is significantly altered in disease. The focus of this review is to summarize current knowledge on the role of galectins in leukocyte trafficking during inflammation and the clinical approaches being taken to target these interactions for treatment of inflammatory disease.

The role of galectins in mediating the adhesion of circulating cells to vascular endothelium

“…There is a rise in research focusing on the development of therapeutic approaches that target galectin-glycan interactions aiming to treat various health conditions ( 2 , 151 – 155 ), including inflammatory disorders ( 156 ), autoimmune diseases ( 157 ), and cancer ( 158 – 160 ). These experimental therapeutics encompass small molecule chemical inhibitors, natural polysaccharides, neutralizing antibodies, and synthetic peptides.…”

“…Although galectin inhibitors show great promise as therapeutics, their specificity and selectivity within a particular pathological condition require further exploration. Systemic treatment may result in nonspecific effects on uninvolved organs or physiologies, potentially diminishing treatment efficacy ( 157 ). Therefore, employing a more targeted delivery approach to affected tissues and cells could enhance the potential for modulating the effects of galectins in vivo without impacting other tissues ( 157 ).…”

“…Systemic treatment may result in nonspecific effects on uninvolved organs or physiologies, potentially diminishing treatment efficacy ( 157 ). Therefore, employing a more targeted delivery approach to affected tissues and cells could enhance the potential for modulating the effects of galectins in vivo without impacting other tissues ( 157 ). A deeper understanding of galectin interactions with circulating cells and ECs, coupled with the ability to manipulate these interactions, could greatly enhance therapeutic strategies and improve patient treatment outcomes.…”

Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators

“…Furthermore, there is influx of plasma proteins containing antibodies and other soluble mediators, such as anaphylatoxins of complement cascade that are crucial for the opsonisation of infectious agents [21] . Concomitantly, the other events that follow are recruitment of leukocytes (mainly phagocytic neutrophils) to the inflamed site [22] ; increase in the expression of cell adhesion molecules (CAM) on circulating leukocytes and venular endothelial cell (ECs), such as selectins(P- and E-selectins).They help in trapping the floating neutrophils and their attachment to endothelial cells, causing leukocyte–endothelial cell adhesion [23] , [24] . The adhesion of neutrophils on EC by selectins is weak and immediately initiates “rolling” of neutrophils [25] .…”

Where the Action Is—Leukocyte Recruitment in Atherosclerosis

“…Recent studies have identified further relevant players, such as the interaction of leukocyte macrophage receptor 1 (Mac-1) with platelet CD147 ( 45 ) in platelet-mediated leukocyte recruitment. In addition to membrane-bound selectins, extracellular matrix proteins, such as galectins, are likely to be involved in the leukocyte adhesion cascade including rolling ( 46 ). Here, extracellular galectins might bind glycosylated ligands on both ECs and leukocytes thus facilitating further interactions.…”