What is leukocyte diapedesis?
Leukocyte diapedesis is the passage of white blood cells into the endothelium of small blood vessels.
The technical term stands for the inner lining of the arteries, venules and capillaries. Movement is always extravascular. Accordingly, the immune cells migrate through the vascular endothelium outside of the blood and lymphatic vessels. For example, leukocyte diapedesis takes place during the recirculation of lymphocytes in lymphatic organs.
The mechanism has not yet been fully elucidated. The purpose of this form of diapedesis is to allow the white blood cells to exit the blood. This allows them to reach infected tissue and initiate the fight against pathogens.
What happens in leukocyte diapedesis?
In the special form of diapedesis, different immune cells emerge from the vessels. These are, for example:
• monocytes ,
• granulocytes ,
• macrophages and
• lymphocytes.
The process ensures that the leukocytes reach the body tissue affected by pathogens. In addition, they initiate an inflammatory process and keep it going. Accordingly, wound healing requires the white blood cells to migrate through the vessel walls.
The migration of immune cells also leads to negative aspects. For example, if they attack the body’s own tissue, you are suffering from an autoimmune disease. In addition, there is a possibility that inflammation will not subside but develop into a chronic disorder.
Scientists are studying leukocyte diapedesis to understand the mechanism that causes leukocytes to leak out of the blood. The extravasation of the white blood cells takes place in several phases.
Cell adhesion molecules and chemical signaling agents work together to scavenge the leukocytes from the bloodstream. They then guide them to the infected body region. Before the immune cells leave the vessels, they adhere to the vessel wall. The inner surface is lined with endothelial cells.
An exact explanation for the penetration of this layer does not yet exist. The leukocytes pass through the endothelial cell network in two different ways. In the paracellular pathway, they move between the opened contacts of the endothelial cells. Furthermore, the white blood cells take the transcellular route, in which they penetrate directly through the cells .
Experiments on mice clarify the mode of action of leukocyte diapedesis
Prof. Dr. Dietmar Vestweber from the Max Planck Institute for Molecular Biomedicine tried to research the immigration of immune cells into the tissue. For this purpose, genetically modified mice were bred, which largely have closed endothelial cell contacts.
A mutation of the main adhesion molecule ensures that an adhesive function does not cease. The corresponding rodents have stabilized endothelial cell contacts. Substances that cause tissue swelling – for example histamine – no longer lead to vascular permeability. This circumstance proves that there is an irreversible closure of the endothelial cell contacts.
Research into leukocyte diapedesis showed that the modified mice had fewer immune cells in their tissues than normal animals. This leads to the conclusion that the route through the endothelial cell junctions is the main route by which the leukocytes exit.
However, there was no change in the migration of naïve lymphocytes into the lymph nodes. The researchers therefore assume that the leukocyte migration in these vessels differs from that in the rest of the body.
Why do the endothelial cell contacts open?
The leukocytes also pass through the endothelial cell network in a paracellular manner. The openings within the association are created by the interaction of the phosphatase VE-PTP and VE-cadherin. This stabilizes the adhesion function. To prove the hypothesis, the researchers again bred genetically modified mice. There was no dissociation of VE-PTP and VE-cadherin in them.
The mutation was intended to inhibit white blood cell migration to tissues outside the blood vessels. The experiment showed that the dissociation of the VE-PTP/VE-cadherin complex is relevant for leukocyte diapedesis.
Prevent diapedesis and relieve inflammation
The migration of immune cells into infected tissue leads to the maintenance of an inflammatory process. If the doctors block this form of diapedesis, they prevent the inflammation. An example is the inhibition of the adhesion mechanisms. These ensure that the lymphocytes attach to the endothelial cells in the central nervous system.
Blocking the mechanism results in an effective therapy for the disease multiple sclerosis. This causes damage to neuronal brain structures due to immigrated lymphocytes.
Furthermore, by curbing the escape of immune cells, there is the possibility of treating psoriasis. Knowledge of the migration of leukocytes into tissue supports new therapies against chronic inflammation. This also includes joint inflammation or a permanent inflammatory state of the thyroid gland.
Leukocyte diapedesis as immune surveillance
The migration of leukocytes to inflamed tissues in your body turns out to be a normal physiological process. The process plays an important role in combating germs and in tissue renewal. In addition, the diapedesis of the lymphocytes ensures a holistic monitoring of your immune system. The white blood cell subset provides an immune response and returns to the vascular system via the lymph. In technical terms, the mechanism of action is called lymphocyte recirculation.
By researching leukocyte migration, there is an option to develop drugs that affect it. Accordingly, intensive research into leukocyte diapedesis ensures the production of medicines that already help to prevent rheumatism and arthritis.
