leukocyte cell-cell adhesion

Definition

Target type: biologicalprocess

The attachment of a leukocyte to another cell via adhesion molecules. [GOC:go_curators]

Leukocyte cell-cell adhesion is a complex and essential process for immune function, allowing white blood cells (leukocytes) to navigate through the bloodstream, migrate to sites of infection or inflammation, and interact with other immune cells. This intricate process involves multiple stages, each mediated by specific adhesion molecules expressed on both leukocytes and the endothelial cells lining blood vessels.

The first step is **tethering**, where leukocytes loosely bind to the endothelium. This initial interaction is mediated by selectins, a family of carbohydrate-binding proteins. Selectins are expressed on both leukocytes and endothelial cells, and they recognize and bind to specific sugar moieties on opposing cells. For example, L-selectin is expressed on leukocytes and binds to GlyCAM-1 and CD34, which are found on endothelial cells. This tethering interaction slows down the leukocyte's movement, allowing for further interactions.

Next comes **rolling**, where leukocytes roll along the endothelium in a "stop-and-go" motion. This rolling is facilitated by the weak, transient binding of selectins, which allows for detachment and rebinding. Rolling allows leukocytes to sample the endothelial surface for potential activation signals.

The third step is **activation**, where leukocytes receive signals from the endothelium that activate their integrins, another family of adhesion molecules. Integrins are heterodimers consisting of α and β subunits. In the resting state, integrins are in a low-affinity state, but upon activation, they undergo a conformational change that increases their binding affinity for their ligands. The signals that activate integrins can be chemokines, pro-inflammatory cytokines, or other soluble factors.

Finally, **firm adhesion** occurs when activated integrins bind to their ligands on the endothelium. These ligands are primarily immunoglobulin superfamily members, such as ICAM-1, ICAM-2, and VCAM-1, which are expressed on endothelial cells. The binding of integrins to these ligands is strong and stable, effectively stopping leukocyte movement.

After firm adhesion, leukocytes undergo **transmigration** through the endothelium, a process known as diapedesis. This movement is facilitated by integrins and other adhesion molecules, as well as by changes in the endothelial cell junctions.

The entire process of leukocyte cell-cell adhesion is tightly regulated and involves multiple signaling pathways and feedback mechanisms. This intricate process ensures that leukocytes are recruited to the appropriate sites of inflammation or infection, while avoiding inappropriate activation and migration. Disruptions to this process can lead to various immune dysfunctions and diseases.'
"

Proteins (17)

Compounds (357)