INFLAMMATION

The traditional three-step leukocyte adhesion cascade involves cell rolling, cell adhesion and cell migration and transmigration.

1.  Cell Rolling:  Selectin-mediated rolling.  Selectins are a family of single-chain transmembrane glycoproteins, expressed on the surface of leukocytes, platelets and activated endothelial cells.  E-selectin, also known as CD62E, is a cell adhesion molecule expressed only on endothelial cells activated by cytokines.  E-selectin recognizes and binds with low affinity to sialylated carbohydrates present on the surface proteins of certain leukocytes, causing the cells to roll along the endothelial surface of the blood vessel, as temporary interactions with exceptionally high on- and off-rates are
established.

Cell-Ligand / Cell-Protein Rolling

2.  Cell Adhesion:  Chemokine-triggered activation and integrin-dependent arrest.  As the inflammatory response progresses, chemokines released by injured tissue enter the blood vessels and activate the rolling leukocytes, which are now able to tightly bind to the endothelial surface, an essential step prior to transmigration towards the inflamed tissue.  Chemokines cause surface integrins to switch from a low-affinity state to a high-affinity state. In the activated state, integrins bind tightly to complementary receptors expressed on endothelial cells.  This promotes the firm adhesion of the leukocytes through integrin-mediated binding, such as VLA-4 that binds to VCAM-1, or LFA-1 to ICAM-1.

3.  Cell Migration & Transmigration:  Intraluminal crawling and paracellular and transcellular migration.

Cell-Ligand / Cell-Protein Adhesion

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