Science: how do neutrophils migrate in inflammation?

May 14, 2015 / BIOON / -- inflammatory response is generally caused by the damage of vascularized tissue, which can achieve the steady-state control of the body by eliminating microorganisms and healing wounds However, uncontrolled inflammation can also lead to pathological changes in the body Therefore, we need to have a systematic understanding of the signaling mechanism in the inflammatory response However, the biggest problem is that the internal signals of inflammatory tissue are complex, which move the whole body by pulling one hair, so it is difficult to find a clear clue McDonald et al Have done a detailed study on the migration process of neutrophils corresponding to inflammatory stimulation First, they used live imaging technology to observe the immune response of mice with tissue damage in real time They stimulated the liver surface of mice with high temperature to produce necrotic apoptosis They found that neutrophils migrated to the site of inflammation within an hour of the injury At first glance, the site of inflammation seems to be homogenized, with both living and dead cells on it It seems that neutrophils don't have the choice to react However, this seemingly homogeneous site contains very complex cytokines, which can directly or indirectly act on neutrophils At the site of inflammation, damaged cells release a class of soluble molecules called damage associated molecular patterns (damps) Damp includes ATP, formylated polypeptide, heat shock protein (HSP), chromatin, galactose lectin, etc Peripheral macrophages can respond to damp signals in many ways, such as by releasing chemokines to further increase the intensity of inflammatory response Finally, this effect leads to the high expression of adhesion molecules on the surface of blood vessels to adsorb lymphocytes Under the action of adhesion molecules, lymphocytes cross the barrier of blood vessels and reach the damaged tissues Some adhesion molecules play an important role in this process, such as beta-2 integrin, which can slow down the flow of lymphocytes in blood vessels and improve their adhesion probability On the one hand, chemokines can be used to activate lymphocytes, on the other hand, they can also attract lymphocytes to migrate to specific sites by forming chemical concentration gradient After that, the author separated all kinds of signals in the process of neutrophil migration in detail through genetics or drug blocking For damp, ATP released by dead cells is a key signal, which can activate purinergic receptors of local macrophages, activate NLRP3 inflammatory bodies in cells and promote the secretion of IL-1 beta IL-1 beta can promote the expression of ICAM-1 in vascular epidermal cells, thus enhancing the adhesion of Mac-1 to neutrophils After that, the adherent neutrophils crawled along the sinusoidal vessels, and were attracted by the concentration gradient of chemokines to move to the necrotic area This signal depends on the chemokine receptor CXCR2 on the surface of neutrophils Although there are many chemotactic gradients in the inflammatory site, neutrophils only respond to a few of them, and the chemokines preferred by neutrophils will also change with the moving to the target location There is no clear explanation for this problem One possibility is that in the early migration process, neutrophils are mainly affected by the inflammatory signals secreted by local macrophages, while when they reach the "border" area, neutrophils mainly rely on their own receptors to sense the external formylated polypeptides to know their migration The authors believe that the signals received by the migration of different lymphocytes (including neutrophils) are specific in different types of injury, different tissues, different times Therefore, the clear classification of these signals can help to treat various types of inflammatory diseases This article is the original compilation of Biovalley Welcome to reprint! Please indicate the source of the reprint and attach the original link For more information, please download Biovalley information app 　　DOI: 10.1126/scisignal.2002051 PMC:
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Sorting the Signals from the Signals in the Noisy Environment of Inflammation
William A Muller
Necrotic cells release dozens, possibly hundreds, of molecules that stimulate the inflammatory response Healthy cells in the environment react to these by secreting other infl ammatory mediators to amplify the response In response to acute necrotic injury in the liver, neutrophils follow a restricted set of molecular cues to move along the sinusoids through the infl amed tissue and into the zone of necrosis, as demonstrated by intravital microscopy to view leukocyte migration
live and in real time Necrosis initiates an intricate interplay between damageassociated molecular pattern molecules, stromal infl ammatory cells, and neutrophils This results in a series of clear molecular signals, enabling neutrophils to follow an intravascular chemokine gradient along the sinusoid in the region where blood still circulates and a formyl peptide gradient through the nonperfused region to the necrotic focus.