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Neutrophils | Cells in Acute Inflammation | Audio Lecture

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▬▬▬▬▬▬▬▬▬▬ Contents of this video ▬▬▬▬▬▬▬▬▬▬
Definition:

• Rolling of neutrophils refers to the process by which neutrophils (a type of white blood cell) adhere to and move along the endothelial cells of blood vessels. This process is a crucial step in the immune response, allowing neutrophils to exit the bloodstream and migrate to sites of infection or inflammation.

• Rolling (or tumbling) is mediated by the action of endothelial selectins loosely binding to leukocytes, producing a characteristic “rolling” movement of the leukocytes along the endothelial surface.

[ ] After Margination, the slowed leukocytes sense signals from the endothelium, resulting first in the cells rolling on the vessel wall and then recognizing adhesion molecules expressed on the endothelium that lead to the cells adhering firmly (resembling pebbles over which a stream runs without disturbing them).

[ ] The attachment of leukocytes to endothelial cells is mediated by adhesion molecules whose expression is enhanced by cytokines, which are secreted by sentinel cells in tissues in response to microbes and other injurious agents.

[ ] The two major families of proteins involved in leukocyte adhesion and migration are the selectins and integrins and their ligands. They are expressed on leukocytes and endothelial cells.

[ ] Selectins: The initial rolling interactions are mediated by selectins, of which there are three types:
• one expressed on leukocytes (L-selectin)
• one on endothelium (E-selectin)
• one in platelets and on endothelium (P-selectin).

[ ] Selectins share a similar molecular structure: a chain of transmembrane glycoproteins with an extracellular lectin-binding domain. This calcium-dependent, or C-type, lectin binds sialylated oligosaccharides, specifically the sialyl-Lewis X moiety, on addressins, which allows rapid cell attachment and rolling.

[ ] ligands for selectins are
• 📍sialylated oligosaccharides
• 📍bound to mucin-like glycoproteins.
• The expression of selectins and their ligands is regulated by cytokine produced in response to infection and injury.

[ ] Within 1 to 2 hours the endothelial cells begin to express E-selectin and the ligands for L-selectin. Other mediators such as histamine and thrombin, stimulate the redistribution of P-selectin from its normal intracellular stores in endothelial cell granules (called Weibel-Palade bodies) to the cell surface.

[ ] Selectins are induced by the cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF). TNF and IL-1 act on the endothelial cells of postcapillary venules induce the coordinate expression of numerous adhesion molecules.

[ ] P-selectin is preformed and stored in Weibel-Pallade bodies of endothelial cells and α-granules of platelets. On stimulation with histamine, thrombin or specific inflammatory cytokines, P-selectin moves rapidly to the cell surface, where it binds sialyl-Lewis X on leukocyte surfaces. Preformed P-selectin can be delivered quickly to the cell surface, allowing rapid adhesive interaction between endothelial cells and leukocytes.

[ ] P-selectins, stored in endothelial Weibel-Palade bodies and platelet alpha granules, relocate to the plasma membrane after stimulation by mediators such as 📍histamine and thrombin

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