Index
The ability to transmigrate is critically important for T lymphocytes at all stages of life.
Diapédesis is the phenomenon whereby, during an inflammation or an immune reaction, specialized leukocytes (eosinophilic granulocytes) adhere to and cross the endothelium of the blood vessels and the underlying matrix.
Function
Diapédesis, also called transmigration, is the process by which T lymphocytes migrate through the venular walls of blood vessels to enter various tissues and organs.
From the entry of T cell precursors into the thymus for T cell development to the entry of naïve T cells into the lymph nodes for the activation or migration of effector T cells into tissues to fight infection.
Multiple steps of lymphocyte diapédesis
Migration of T lymphocytes occurs through a multistep pathway.
Each step of diapédesis is regulated by the interactions that occur between chemokine receptors that are expressed on the surface of lymphocytes and their ligands, which in turn are expressed on endothelial cells that line the vascular walls.
Diapédesis occurs through a multistep pathway that includes lymphocyte lamination, signaling, firm adhesion, and transmigration .
Lymphocyte lamination
Lymphocyte lamination initiates contact between the lymphocytes and the endothelium.
It is mediated by repeated binding release events between selectins and their ligands.
When the lamination process is carried out, the chemokines that are presented in the endothelial cells manage to interact with the chemokine receptors located on the surface of the lymphocytes.
Signage
The interaction between a chemokine and its chemokine receptor leads to an intracellular signaling event, which in turn activates the adhesion molecules of the integrin family.
Firm adherence
When activation occurs, the integrins express high-affinity binding areas that interrelate with the cell adhesion molecules that are present in the vascular walls, causing lymphocyte dilation and firmer adhesion.
Diapédesis
The transmigration process is less characterized compared to the other steps, especially with a focus on T lymphocytes, however, some information is known from experiments with other cell types, such as neutrophils.
To find a suitable position to cross the endothelium, firmly attached leukocytes crawl toward an intercellular junction in the endothelium and then transmigrate to or even through the intercellular matrix in an integrin-mediated process.
Diapédesis process
Diapédesis can occur either by migration across the junction between adjacent endothelial cells or through a transcellular channel through a single endothelial cell.
Certain homophilic adhesion molecules (ie, adhesion molecules that bind to each other) present at the intercellular junction of the endothelium are involved in leukocyte migration.
These molecules include platelet and endothelial cell adhesion molecules 1, binding adhesion molecules A, B, and C, intracellular adhesion molecules 1 and 2, and the CD99 glycoprotein molecule.
After traversing the endothelium, the leukocytes are temporarily delayed in their journey through the continuous basement membrane of the venules, but eventually the cells pierce the basement membrane, probably secreting collagenases.
Once leukocytes enter extravascular connective tissue, they are able to adhere to the extracellular matrix by virtue of β1 integrins (ITGB1) and the binding of CD44 to matrix proteins.
The net result of this process is that leukocytes, by the action of chemokines, stimulate cells to rapidly accumulate where they are needed, migrating through the interendothelial spaces in favor of the chemical concentration gradient, to the site of injury. or infection.
The binding of selectins to their ligands has a fast rate but also has a fast deactivation rate and is of low affinity.
This property allows selectins to mediate the initial binding and subsequent lamination of leukocytes in the endothelium against the bloodstream.
Leukocytic diapedesis occurs mainly in the venules and in the case of the lungs, it also occurs in the capillaries.