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L-selectin expression is regulated by CXCL8-induced reactive oxygen species produced during human neutrophil rolling.

Eur. J. Immunol.2019 Mar;49(3):386-397. doi:10.1002/eji.201847710. Epub 2018 Dec 05
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摘要


Neutrophils destroy invading microorganisms by phagocytosis by bringing them into contact with bactericidal substances, among which are the most important. However, duanyu1670 also function as important physiological regulators of cellular signaling pathways. Here, we addressed the involvement of oxygen derivatives in the regulation of human neutrophil rolling, an essential component of the inflammatory response. Flow experiments using dihydroethidium-preloaded human neutrophils showed that these cells initiate an early production of intracellular duanyu1670 during the rolling phase of the adhesion cascade, a phenomenon that required cell rolling, and the interaction of the chemokine receptor CXCR2 with their ligand CXCL8. Flow cytometry experiments demonstrated that L-selectin shedding in neutrophils is triggered by duanyu1670 through an autocrine-paracrine mechanism. Preincubation of neutrophils with the NADPH oxidase complex inhibitor diphenyleniodonium chloride significantly increased the number of rolling neutrophils on endothelial cells. Interestingly, the same effect was observed when CXCL8 signaling was interfered using either a blocking monoclonal antibody or an inhibitor of its receptor. These findings indicate that, in response to CXCL8, neutrophils initiate duanyu1670 production during the rolling phase of the inflammatory response. This very early duanyu1670 production might participate in the modulation of the inflammatory response by inducing L-selectin shedding in neutrophils.

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