diapedesis

Phenomenon by which during an inflammation or immune reaction, specialized leukocytes (eosinophilic granulocytes) adhere to and pass through the endothelium of the blood vessels and the underlying matrix.

The reaction passes through the following steps:

 0. Binding leukocytes-epithelial cells

The flow of cells is slowed down by first making contacts to the endothelium via P-selectin (SELP), E-selectin (SELE), and L-selectin (SELL) and their receptors. The selectins (SELs) all function in adhesion of leukocytes to endothelial cells. The binding of selectins to their ligands has a fast on rate but also has a fast off rate and is of low affinity; this property allows selectins to mediate initial attachment and subsequent rolling of leukocytes on endothelium in the face of flowing blood.

 1. Rolling

 2. Adhesion

After activation of leukocyte integrins, firm contacts are established between them and endothelium molecules of the Ig superfamily - LFA-1, Mac-1, VLA-4 etc.

 3. Flattening of the cells and diapedesis

Adhering leukocytes crawl to an intercellular junction of the endothelium and then transmigrate to or even through the intercellular matrix. This is mediated by a homophilic interactions of PECAM and CD31.

Chemokines act on the adherent leukocytes and stimulate the cells to migrate through interendothelial spaces toward the chemical concentration gradient, that is, toward the site of injury or infection.

Certain homophilic adhesion molecules (i.e., adhesion molecules that bind to each other) present in the intercellular junction of endothelium are involved in the migration of leukocytes.

One of these molecules is a member of the immunoglobulin superfamily called PECAM-1 (platelet endothelial cell adhesion molecule) or CD31.

Leukocytic diapedesis, similar to increased vascular permeability, occurs predominantly in the venules (except in the lungs, where it also occurs in capillaries).

After traversing the endothelium, leukocytes are transiently retarded in their journey by the continuous basement membrane of the venules, but eventually the cells pierce the basement membrane, probably by secreting collagenases.

The net result of this process is that leukocytes rapidly accumulate where they are needed.

Once leukocytes enter the extravascular connective tissue, they are able to adhere to the extracellular matrix by virtue of β1 integrins (ITGB1) and CD44 binding to matrix proteins. Thus, the leukocytes are retained at the site where they are needed.

Videos

 lymphocyte homing to a wounded area

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 Neutrophils going to the site of infection

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 Neurophil rolling

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References

 Robbins