Selectins – different types and functions

Selectins are essentially classified as a carbohydrate binding transmembrane family of molecules which are often associated to the surfaces of platelets, leukocytes and endothelial cells. In the absence of selectins there is often significant consequences to health, where persistent bacterial or disease infections are occurring and in many cases are recurrent. This is due to the fact that one of the major roles of selectins or their ligands is to aid the trafficking of T-lymphocytes, platelets and the innate immune cells. When the process of inflammation occurs, selectins are essential for the leukocyte to initially attach and this process is critical in order to activate the downstream movement (referred to as leukocyte rolling).

At present there are 3 different types of selectins that have been identified: L-selectin, E-selectin and P-selectin.

• L-selectin: Expressed on monocytes, lymphocytes and granulocytes.
• E-selectin: Expressed on activated endothelium and can be induced via inflammatory cytokines.
• P-selectin: Expressed on platelets and activated endothelial cell surfaces.

L-selectin

L-selectin is the smallest of the selectins, a glycoprotein of approx. 75-100 kDa and play’s a major function in adhesion to endothelial cells and lymphocyte homing especially in peripheral lymph nodes. It has an important role in the initial capture of leukocyte which occurs during the early steps of the adhesion cascade process. After this process has completed L-selectin is then shed from the leukocyte surface. Many research publication have indicated the importance of L-selectin in mediating the process of leukocyte rolling (especially after surgery) and its importance in the recruiting neutrophils during inflammation. However, both L- and P-selectin need to be present in order to allow the process of leukocyte capture to occur. L-selectin is not able to carry out this process alone and requires the co-operation of P-selectin before the rolling process can proceed.

E-selectin

E-selectin is expressed on the surfaces of inflamed vascular endothelial cells which is in response to IL-1beta and TNF-alpha. It is a glycoprotein that is 110-115 kDa in size and play an important role in adhesion and mediating leukocyte rolling. Studies have indicated where there is a lack of E-selectin this can result in reduced levels of leukocyte adhesion being experience in response to cytokine or chemoattactant stimulation.

P-selectin

P-selection represent the largest of the selectin family member which is around 140 kDa in size and is predominately expressed in granules of activated endothelial and platelets cells. IL-1 and TNF have been discovered to trigger additional synthesis of P-selectin. Inflammatory mediators for example histamine or thrombin are known to stimulate endothelial cells which results in P-selectin being expressed on the cell surface. One of the main ligand present on the cell surface is P-selectin glycoprotein ligand-1 (PSGL-1), this is present on all leukocyte cells and the interaction between P-selectin and PSGL-1 is essential in order to medicate the process of leukocyte rolling on the venular endothelium.

Further Readings

https://www.ncbi.nlm.nih.gov/pubmed/29272415

http://www.cryst.bbk.ac.uk/pps97/assignments/projects/emilia/Adh_mol.HTM

https://en.wikipedia.org/wiki/Selectin

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