Inflammation is a necessary step involved in the immune response, allowing our bodies to fight and eliminate disease, allergies, and injuries. The inflammatory response recruits several mediators to aid in the destruction of whatever pathogen caused the response in the first place. Cells such as leucocytes, eosinophils, and neutrophils get recruited to the site in order to assist. Once leucocytes are in the area, these cells can release molecules that destroy infections.1 Hence, hindering recruitment prevents much-needed molecules from doing their jobs.
The Role of FUT7 in Inflammation
Leukocyte recruitment is mediated via cell adhesion molecules (CAMs) called selectins, which are glycoproteins that bind to sugar molecules. These chains of oligosaccharides allow for the essential adhesion of leukocytes to endothelial cells that must occur during the inflammatory response. Specifically, P-and E-selectins expressed by endothelial cells interact with leukocyte receptors to facilitate linkage.2
In order to create selectin proteins, glycosylation reactions catalyzed by fucosyltransferases must take place. One particular fucosyltransferase, α(1,3)fucosyltransferase (Fuc-TVII, or FUT7), is expressed in leukocytes and eosinophils. Studies have found that the enzyme plays a crucial role in recruitment and when deficient, the extravasation is impaired.2 This could be detrimental to the acute inflammatory response.
On the other hand, in diseases where inflammation is more chronic and part of the problem instead of the solution, it’s beneficial to find inhibitors to the proteins involved in the immune response. FUT7 is an exemplary candidate. Chronic inflammation contributes to the following diseases:
- chronic peptic ulcer
- rheumatoid arthritis
- ulcerative colitis and Crohn’s disease
- active hepatitis
The universal detection of GDP can be obtained by the Transcreener GDP Assay allowing measurement of Fut7 activity. Fucosyltransferase assays can, therefore, assist in the discovery of novel molecules that can inhibit and potentially be used for therapeutic purposes. Benefits and further instruction regarding the activity assay can be found here. Briefly, the nature of a fucosyltransferase is to assist in the transfer of a fucose sugar from a GDP-fucose (guanosine diphosphate-fucose) donor substrate to an acceptor substrate, forming GDP as a product which can be measured by using specific antibody labeled with a fluorophore. This assay has the capability of testing thousands of wells in a high throughput format, making it ideal for drug discovery.
- Khilanani, P., Chou, T., & Kessel, D. (1978). Guanosine Diphosphate-t-Fucose Plasma : N-Acetylglucosaminide Fucosyltransferase as in Index of Bone Marrow Hyperplasia after, (JANUARY), 181–184. https://cancerres.aacrjournals.org/content/canres/38/1/181.full.pdf
- Satoh, T., Kanai, Y., Wu, M., Yokozeki, H., Kannagi, R., Lowe, J. B., & Nishioka, K. (2005). Dependent Eosinophil Selectin Ligand and Recruitment to the Skin, 167(3), 1–5. https://www.ncbi.nlm.nih.gov/pubmed/16127157