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Leukocyte extravasation
In immunology, leukocyte extravasation (also commonly known as leukocyte adhesion cascade or diapedesis – the passage of cells through the intact vessel wall) is the movement of leukocytes (white blood cells) out of the circulatory system (extravasation) and towards the site of tissue damage or infection. This process forms part of the innate immune response, involving the recruitment of non-specific leukocytes. Monocytes also use this process in the absence of infection or tissue damage during their development into macrophages.
Leukocyte extravasation occurs mainly in post-capillary venules, where haemodynamic shear forces are minimised. This process can be understood in several steps:[citation needed]
It has been demonstrated that leukocyte recruitment is halted whenever any of these steps is suppressed.
White blood cells (leukocytes) perform most of their functions in tissues. Functions include phagocytosis of foreign particles, production of antibodies, secretion of inflammatory response triggers (histamine and heparin), and neutralization of histamine. In general, leukocytes are involved in the defense of an organism and protect it from disease by promoting or inhibiting inflammatory responses. Leukocytes use the blood as a transport medium to reach the tissues of the body. Here is a brief summary of each of the four steps currently thought to be involved in leukocyte extravasation:
Upon recognition of and activation by pathogens, resident macrophages in the affected tissue release cytokines such as IL-1, TNFα and chemokines. IL-1, TNFα and C5a cause the endothelial cells of blood vessels near the site of infection to express cellular adhesion molecules, including selectins. Circulating leukocytes are localised towards the site of injury or infection due to the presence of chemokines.[citation needed]
Like velcro, carbohydrate ligands on the circulating leukocytes bind to selectin molecules on the inner wall of the vessel, with marginal affinity. This causes the leukocytes to slow down and begin rolling along the inner surface of the vessel wall. During this rolling motion, transitory bonds are formed and broken between selectins and their ligands.
For example, the carbohydrate ligand for P-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), is expressed by different types of leukocytes (white blood cells). The binding of PSGL-1 on the leukocyte to P-selectin on the endothelial cell allows for the leukocyte to roll along the endothelial surface. This interaction can be tuned by the glycosylation pattern of PSGL-1, such that certain glycovariants of PSGL-1 will have unique affinities for different selectins, allowing in some cases for cells to migrate to specific sites within the body (e.g. the skin).
At the same time, chemokines released by macrophages activate the rolling leukocytes and cause surface integrin molecules to switch from the default low-affinity state to a high-affinity state. This is assisted through juxtacrine activation of integrins by chemokines and soluble factors released by endothelial cells. In the activated state, integrins bind tightly to complementary receptors expressed on endothelial cells, with high affinity. This causes the immobilization of the leukocytes, which varies in vessels that contain different shear forces of the ongoing blood flow.[citation needed]
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Leukocyte extravasation
In immunology, leukocyte extravasation (also commonly known as leukocyte adhesion cascade or diapedesis – the passage of cells through the intact vessel wall) is the movement of leukocytes (white blood cells) out of the circulatory system (extravasation) and towards the site of tissue damage or infection. This process forms part of the innate immune response, involving the recruitment of non-specific leukocytes. Monocytes also use this process in the absence of infection or tissue damage during their development into macrophages.
Leukocyte extravasation occurs mainly in post-capillary venules, where haemodynamic shear forces are minimised. This process can be understood in several steps:[citation needed]
It has been demonstrated that leukocyte recruitment is halted whenever any of these steps is suppressed.
White blood cells (leukocytes) perform most of their functions in tissues. Functions include phagocytosis of foreign particles, production of antibodies, secretion of inflammatory response triggers (histamine and heparin), and neutralization of histamine. In general, leukocytes are involved in the defense of an organism and protect it from disease by promoting or inhibiting inflammatory responses. Leukocytes use the blood as a transport medium to reach the tissues of the body. Here is a brief summary of each of the four steps currently thought to be involved in leukocyte extravasation:
Upon recognition of and activation by pathogens, resident macrophages in the affected tissue release cytokines such as IL-1, TNFα and chemokines. IL-1, TNFα and C5a cause the endothelial cells of blood vessels near the site of infection to express cellular adhesion molecules, including selectins. Circulating leukocytes are localised towards the site of injury or infection due to the presence of chemokines.[citation needed]
Like velcro, carbohydrate ligands on the circulating leukocytes bind to selectin molecules on the inner wall of the vessel, with marginal affinity. This causes the leukocytes to slow down and begin rolling along the inner surface of the vessel wall. During this rolling motion, transitory bonds are formed and broken between selectins and their ligands.
For example, the carbohydrate ligand for P-selectin, P-selectin glycoprotein ligand-1 (PSGL-1), is expressed by different types of leukocytes (white blood cells). The binding of PSGL-1 on the leukocyte to P-selectin on the endothelial cell allows for the leukocyte to roll along the endothelial surface. This interaction can be tuned by the glycosylation pattern of PSGL-1, such that certain glycovariants of PSGL-1 will have unique affinities for different selectins, allowing in some cases for cells to migrate to specific sites within the body (e.g. the skin).
At the same time, chemokines released by macrophages activate the rolling leukocytes and cause surface integrin molecules to switch from the default low-affinity state to a high-affinity state. This is assisted through juxtacrine activation of integrins by chemokines and soluble factors released by endothelial cells. In the activated state, integrins bind tightly to complementary receptors expressed on endothelial cells, with high affinity. This causes the immobilization of the leukocytes, which varies in vessels that contain different shear forces of the ongoing blood flow.[citation needed]