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Selectins are rod-like cell surface glycoproteins composed of an N-terminal lectin domain, an epidermal growth factor (EGF) domain, and sequence-conserved repeats (SCR domains) that vary from two to nine depending on selectin type. The lectin domain binds carbohydrates in the presence of calcium ions, while the EGF domain regulates binding specificity and strength.

L-selectins are expressed on immune cells like lymphocytes and help them migrate into lymph nodes. P-selectins are larger and primarily expressed on platelets, aiding in platelet and immune cell aggregation at injury sites. E-selectins are temporally expressed on endothelial cells during immune responses, working alongside P-selectins to slow free-flowing leukocytes.

During inflammation, endothelial cells rapidly mobilize P-selectins from Weibel-Palade bodies to their surface and upregulate E-selectin and P-selectin genes. These selectins catch free-flowing leukocytes expressing carbohydrate ligands like PSGL-1, initially binding weakly. Shear stress triggers selectins to open, enabling strong binding that slows leukocytes, allowing other cell adhesion molecules to recruit them to appropriate tissues through leukocyte homing.

Selectins form weak, transient cell-cell adhesion by binding carbohydrate ligands on cells of different tissue types, such as between neutrophils and endothelial cells. This temporary interaction allows leukocytes to roll along the endothelial surface without permanent attachment, enabling them to be recruited to appropriate tissue microenvironments rather than forming stable cell-cell connections.

Metastatic cancer cells express carbohydrate ligands on their cell surface, making them receptive to binding endothelial selectins. This hijacking of the normal selectin-mediated recruitment process allows cancer cells to escape blood vessels through extravasation and infiltrate new tissues, producing secondary tumors at distant sites.

Selectins initially exist in a closed conformation, binding weakly to their carbohydrate ligands. As leukocytes flow along the endothelial surface, the shear stress generated by these interactions triggers selectins to open into a conformation that enables strong binding, effectively slowing down the free-flowing leukocytes.

Selectins contain a C-type lectin domain that binds carbohydrates only in the presence of calcium ions. This calcium-dependent binding mechanism is critical for selectin recognition of carbohydrate ligands on target cells, enabling the initial weak interactions that initiate leukocyte capture and subsequent recruitment during immune responses.