leukocyte adhesive activation

Definition

Target type: biologicalprocess

The activation of loosely bound or rolling leukocytes by signals displayed on blood vessel endothelial cells, which is typically the second step in cellular extravasation. [ISBN:0781735149, PMID:14680625, PMID:14708592, PMID:7507411, PMID:8600538]

Leukocyte adhesive activation is a crucial process in the immune response, enabling leukocytes (white blood cells) to migrate from the bloodstream into tissues where they are needed to combat infection or injury. This complex process involves a series of coordinated events, including:

1. **Chemotaxis:** Leukocytes are attracted to the site of inflammation by chemical signals called chemokines. These signals bind to specific receptors on the leukocyte surface, triggering a cascade of intracellular signaling events that lead to changes in cell shape and movement.

2. **Rolling Adhesion:** As leukocytes approach the inflamed area, they begin to interact with the endothelial cells lining the blood vessels. This initial interaction is mediated by selectins, a family of adhesion molecules expressed on both leukocytes and endothelial cells. The selectins bind to specific carbohydrate ligands on the opposing cell type, resulting in a weak, rolling adhesion that slows the leukocyte down.

3. **Tight Adhesion:** As leukocytes continue to roll along the endothelium, they encounter a second set of adhesion molecules called integrins. These molecules are normally in an inactive state, but they become activated by chemokine signaling and other stimuli. Upon activation, integrins bind to their ligands, which are typically members of the immunoglobulin superfamily (ICAMs), on the endothelial cell surface. This interaction results in a firm, tight adhesion that prevents the leukocyte from being washed away by the blood flow.

4. **Diapedesis:** Once tightly adhered to the endothelium, leukocytes undergo a process called diapedesis, in which they squeeze between endothelial cells and enter the surrounding tissue. This process is facilitated by a number of factors, including the breakdown of the endothelial cell junction, changes in the cytoskeleton of the leukocyte, and the action of enzymes that degrade the extracellular matrix.

5. **Migration to Site of Inflammation:** After entering the tissue, leukocytes continue to migrate towards the source of inflammation, guided by chemokine gradients. This migration is driven by changes in the cytoskeleton and the coordinated action of motor proteins that propel the cell forward.

Leukocyte adhesive activation is a tightly regulated process that ensures that leukocytes are recruited to the appropriate sites of inflammation in a timely and efficient manner. Dysregulation of this process can lead to a number of pathological conditions, including chronic inflammation, autoimmune diseases, and sepsis.'
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Proteins (1)

Compounds (3)