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Mysterious chemical guidance: Why are white blood cells attracted to the site of infection?
In the human immune system, the function of white blood cells is critical, especially in response to infection and tissue damage. When bacteria or viruses invade, white blood cells quickly gather at the infected site through a process called leukocyte extravasation. This process is not only central to the immune response, but also reveals the important role of chemicals in directing action against infection.
Leukocyte extravasation mainly occurs in post-capillary veins, where the blood flow shear force is smaller, allowing leukocytes to retain and adhere to the vascular endothelium more effectively. Studies have shown that this process is divided into four main steps: chemical attraction, rolling adhesion, tight adhesion, and transfer across the endothelium.
“Once infected, local macrophages will release cytokines, such as IL-1 and TNFα, which stimulate endothelial cells to express adhesion molecules, which paves the way for leukocyte infiltration.”
Chemical Attraction
This stage is first responsible for macrophages in the tissue. When pathogens are recognized, they release cytokines that prompt nearby endothelial cells to express cell adhesion molecules, including selectins. With the release of chemical hormones such as C5a, white blood cells are directed to the site of injury or infection.
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During the rolling adhesion phase, some carbohydrate ligands on the surface of leukocytes bind to selectins in endothelial cells with lower affinity, similar to Velcro. This binding causes the white blood cells to slow down and start rolling along the lining of the blood vessels on the surface of the endothelial cells. During the rolling process, random binding and dissociation occurs between the selectin and its ligand, further bringing the white blood cells closer to the infected area.
Tightly adhered
As the process progresses, chemical signals that promote leukocyte penetration begin to activate the rolling leukocytes, changing the affinity of the integrins on their surfaces from low to high. Such a performance allows integrins upstream and downstream of white blood cells to tightly adhere to the surface of endothelial cells, completing the strengthening of adhesion and making white blood cells begin to become immobile.
Transfer across endothelium
When leukocytes next prepare to cross the vascular endothelium, their cytoskeleton is reorganized, causing the leukocytes to spread out on the endothelial cells and penetrate the spaces between the endothelial cells as pseudopods. This process is called "leukocyte infiltration." Once successfully crossing the endothelium, the leukocytes enter the interstitial space and move along the chemical gradient toward the damaged site.
"This process demonstrates that the body's response to infection is not just rapid, but finely regulated, a biophysical process composed of multiple steps."
Cytohormones and extravasation process
Cytohormones play a crucial role in this process. Not only do they regulate vascular permeability, but they also promote interactions between white blood cells. The release of cytokines such as IL-1 and TNFα allows white blood cells to do their job at the right time and in the right place.
Leukocyte adhesion defect and neutrophil insufficiency
Leukocyte adhesion deficiency (LAD) is a hereditary disease in which leukocytes are unable to successfully adhere to and penetrate the endothelium due to a defect in the integrin β2 chain, resulting in patients often suffering from bacterial infections. At the same time, in some diseases such as sepsis, the extravasation process of white blood cells can become uncontrollable, causing further damage to the body.
Latest developments
In recent years, the emergence of microfluidic devices has allowed researchers to delve deeper into the interaction between leukocytes and endothelial cells and analyze leukocyte extravasation behavior under different fluid conditions. These studies not only improve our understanding of immune response mechanisms, but may also provide new ideas for the development of new drugs, such as treatment options for neutrophil insufficiency.
In this mysterious biological process, white blood cells can be guided to the site of infection so efficiently. Are there other undiscovered mechanisms supporting their actions?
