29.5: Selectins
Cell adhesion is an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which is a C-type lectin that binds carbohydrates only in the presence of calcium ions. Three major types of selectins are identified based on their tissue specificity and length – L-selectins, P-selectins, and E-selectins.
Selectins in Immune Response
The endothelial cells lining the blood vessels express P-selectins and store them in the vesicular bodies called Weible-Palade bodies. During inflammation, histamine stimulation rapidly mobilizes these vesicles to the cell surface. These activated endothelial cells also upregulate their E-selectin and P-selectin genes, thus priming them to recruit free-flowing leukocytes from the bloodstream.
Leukocytes, such as neutrophils and eosinophils, express the carbohydrate ligands, such as PSGL-1, on their cell surface. The long selectins protruding from the endothelial cells can easily interact with these ligands and "catch" the free-flowing leukocytes from the bloodstream. Selectins are initially in the closed conformation, and therefore bind weakly to their ligands. However, as the leukocyte flows along, the shear stress of these interactions triggers the selectins to open. Selectins in open conformation can bind strongly to their ligands and thus, help slow down the leukocytes.
Selectins in Cancer
Metastatic cancer cells hijack the normal selectin-mediated recruitment process to invade healthy tissues. These metastatic cells express the carbohydrate ligands on their cell surface and thus become receptive to bind the endothelial cells. Upon binding, the cancer cells can escape the blood vessel, through a process called extravasation. The cancerous cells can then infiltrate the new site, producing secondary tumors.
