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The rolling journey of white blood cells: What is the secret behind their "rolling" in blood vessels?
In immunology, leukocyte extravasation, or the leukocyte adhesion cascade, is the process by which white blood cells (leukocytes) move from the circulation to sites of tissue damage or infection. This process is an important component of the innate immune response and primarily involves nonspecific recruitment of leukocytes. Monocytes also use this process to develop into macrophages in the absence of infection or tissue damage.
Process Overview
Leukocyte infiltration mainly occurs in the post-capillary veins, where the dynamic shear force of blood flow is reduced, promoting the infiltration of leukocytes. The whole process can be divided into several steps:
- Chemical attraction
- Scroll attachment
- Closely attached
- Transendothelial migration
When any of these steps is inhibited, recruitment of white blood cells is halted. White blood cells perform their functions primarily in tissues, including phagocytosis of foreign particles, production of antibodies, secretion of inflammatory response triggers (such as histamine and heparin), and their neutralization. Overall, white blood cells play an important role in protecting the organism from disease.
Chemical attraction
Once recognized and activated by pathogens, macrophages in damaged tissues release cytokines such as IL-1, TNFα, and chemokines. These factors cause endothelial cells adjacent to the site of infection to express cell adhesion molecules (such as selectins) and direct circulating leukocytes to relocate to the site of injury or infection.
Scroll Attachment
Leukocytes attach to the blood vessel lining like sticky hooks and attach selectin molecules, which causes the leukocytes to slow down and begin rolling along the endothelial surface.
During this rolling process, transient connections are formed and broken between leukocytes and endothelial selectins and their ligands. Such interactions can be modulated by the glycosylation pattern of PSGL-1, such that certain sugar variants have different affinities, allowing leukocytes to migrate to specific body sites, such as the skin.
Closely attached
At the same time, the chemokines released by macrophages activate these rolling white blood cells, causing the integrin molecules on their surface to change from a low-affinity state to a high-affinity state. These integrins bind tightly and with high affinity to ligands specifically expressed on endothelial cells, thereby fixing the approximate location of leukocytes on endothelial cells.
Transendothelial migration
During penetration, the leukocyte cytoskeleton is reorganized, allowing the leukocyte to unfold on the endothelial cells and form pseudopodia, passing through the intercellular spaces of the endothelium. This process is called diapedesis. Once across the endothelium, the leukocytes also need to penetrate the basement membrane.
The entire process of vascular escape is called exudation, and white blood cells migrate along the chemical chemotactic gradient in the interstitial fluid toward the site of injury or infection.
Molecular Biology
The diapedesis process of leukocytes can be summarized into several stages: approach, capture, rolling, activation, binding, binding enhancement and extension, crawling within blood vessels, and transcellular migration or transmigration. The expression of selectins is closely related to the activity of cell adhesion molecules.
Selectins and Integrins
Selectins are expressed after activation of vascular endothelial cells, mainly including P-selectin and E-selectin, which will bind to the glycoprotein chains of white blood cells. Integrins are mainly expressed on white blood cells, where they bind to the adhesion molecules of endothelial cells and temporarily stop the movement of white blood cells.
Cytokines
The exudative process is regulated by the background inflammatory response of cytokines, which induce vasodilation and reduce the charge of the vessel surface, making intermolecular binding with leukocytes easier.
Recent Progress
In recent decades, the advent of microfluidic devices has provided better tools for studying leukocyte-endothelial interactions. These new platforms can simulate more realistic physiological environments, facilitating further exploration of the behavior of white blood cells.
Studies have shown that white blood cells exhibit a peculiar behavior under high shear conditions, a phenomenon known as the "capture bond hypothesis." This means that under certain conditions, high shear forces can enhance the binding force between leukocytes and endothelial cells.
ConclusionAlthough the movement and infiltration of white blood cells in the body seem normal, there are countless complex biochemical processes and mechanisms behind them. These sensitive responses to the environment not only protect our bodies, but also reveal the mysteries of how life works. Can all of this be further optimized so that we can make greater progress in medical technology in the future?
