Examining the role of endothelial derived galectins in vascular inflammation

Lightfoot, Abbey ORCID: 0000-0003-4333-1902 (2024). Examining the role of endothelial derived galectins in vascular inflammation. University of Birmingham. Ph.D.

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Abstract

This thesis explores how galectins, sugar-binding proteins, influence leukocyte trafficking during inflammation. Galectins (Gal) are known to be involved in inflammation, but specific endothelial-galectin interactions remain unclear.

We investigated how inflammatory mediators and shear stress affect the production of endothelial galectins and found that Gal-9 was highly produced in response to virus-associated inflammatory mediators. In contrast, Gal-3 (Gal-3) was downregulated under the same conditions. Interestingly, blood flow patterns also influenced galectin production.

We studied the function of galectins using Gal-knockout mice for intravital microscopy to study leukocyte trafficking events in the absence of galectins, which we then mimicked using in vitro flow assays using siRNA-to knockdown galectin expression in human umbilical vein endothelial cells (HUVEC). Our results suggest that Gal-3 and Gal-9 have distinct roles in leukocyte trafficking. Finally, we used a galectin-peroxidase fusion protein to proximity label Gal-3 interactors on HUVEC in response to cytokine treatment, for downstream identification of novel interactors through mass spectrometry and validation experiments.

Overall, we show that galectins are emerging as complex glycan-binding proteins with context-dependent functions, presenting a rich area for further exploration into their contributions to immune homeostasis and potential therapeutic opportunities, particularly targeted to leukocyte-endothelial interactions.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):