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dc.contributor.authorXu, Yuanfu
dc.contributor.authorLoison, Fabien
dc.contributor.authorLuo, Hongbo
dc.date.accessioned2014-10-30T14:28:30Z
dc.date.issued2010
dc.identifier.citationXu, Yuanfu, Fabien Loison, and Hongbo R. Luo. 2010. "Neutrophil Spontaneous Death Is Mediated by Down-Regulation of Autocrine Signaling through GPCR, PI3K\(\gamma\), ROS, and actin." Proceedings of the National Academy of Sciences 107(7): 2950-2955. doi:10.1073/pnas.0912717107.en_US
dc.identifier.issn1091-6490en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13320258
dc.description.abstractNeutrophil spontaneous apoptosis plays a crucial role in neutrophil homeostasis and the resolution of inflammation. We previously established Akt deactivation as a key mediator of this tightly regulated cellular death program. Nevertheless, the molecular mechanisms governing the diminished Akt activation were not characterized. Here, we report that Akt deactivation during the course of neutrophil spontaneous death was a result of reduced PtdIns(3,4,5)P3 level. The phosphatidylinositol lipid kinase activity of \(PI3K\gamma\), but not class IA PI3Ks, was significantly reduced during neutrophil death. The production of PtdIns(3,4,5)P3 in apoptotic neutrophils was mainly maintained by autocrinely released chemokines that elicited \(PI3K\gamma\) activation via G protein–coupled receptors. Unlike in other cell types, serum-derived growth factors did not provide any survival advantage in neutrophils. \(PI3K\gamma\), but not class IA PI3Ks, was negatively regulated by gradually accumulated ROS in apoptotic neutrophils, which suppressed \(PI3K\gamma\) activity by inhibiting an actin-mediated positive feedback loop. Taken together, these results provide insight into the mechanism of neutrophil spontaneous death and reveal a cellular pathway that regulates PtdIns(3,4,5)P3/Akt in neutrophils.en_US
dc.language.isoen_USen_US
dc.publisherProceedings of the National Academy of Sciencesen_US
dc.relation.isversionofdoi:10.1073/pnas.0912717107en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2840335/en_US
dash.licenseLAA
dc.subjectreactive oxygen speciesen_US
dc.subjectapoptosisen_US
dc.subjectAkten_US
dc.titleNeutrophil Spontaneous Death Is Mediated by Down-Regulation of Autocrine Signaling through GPCR, PI3K\(\gamma\), ROS, and actinen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dash.depositing.authorLuo, Hongbo
dc.date.available2014-10-30T14:28:30Z
dc.identifier.doi10.1073/pnas.0912717107*
dash.contributor.affiliatedLoison, Fabien
dash.contributor.affiliatedLuo, Hongbo


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