Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.

dc.contributor.authorMao, Hui
dc.contributor.authorKano, Gen
dc.contributor.authorHudson, Sherry A.
dc.contributor.authorBrummet, Mary
dc.contributor.authorZimmermann, Nives
dc.contributor.authorZhu, Zhou
dc.contributor.authorBochner, Bruce S.
dc.date.accessioned2014-04-03T11:04:17Z
dc.date.available2014-04-03T11:04:17Z
dc.date.issued2013-06-28
dc.descriptionPMC3695997en_US
dc.description.abstractAbstract BACKGROUND: Siglec-F and Siglec-8 are functional paralog proapoptotic cell surface receptors expressed on mouse and human eosinophils, respectively. Whereas Siglec-8 mediated death involves caspases and/or reactive oxygen species (ROS) generation and mitochondrial injury, very little is known about Siglec-F-mediated signaling and apoptosis. Therefore the objective of the current experiments was to better define apoptosis pathways mediated by Siglec-F and Siglec-8. Given that Siglec-F-induced apoptosis is much less robust than Siglec-8-induced apoptosis, we hypothesized that mechanisms involved in cell death via these receptors would differ. METHODS: Consequences of engagement of Siglec-F on mouse eosinophils were studied by measuring ROS production, and by performing apoptosis assays using eosinophils from normal, hypereosinophilic, NADPH oxidase-deficient, src homology domain-containing protein tyrosine phosphatase (SHP)-1-deficient, and Lyn kinase-deficient mice. Inhibitors of caspase and Src family kinase activity were also used. RESULTS: Engagement of Siglec-F induced mouse eosinophil apoptosis that was modest in magnitude and dependent on caspase activity. There was no detectable ROS generation, or any role for ROS, NADPH oxidase, SHP-1, or Src family kinases in this apoptotic process. CONCLUSIONS: These data suggest that Siglec-F-mediated apoptosis is different in both magnitude and mechanisms when compared to published data on Siglec-8-mediated human eosinophil apoptosis. One likely implication of this work is that models targeting Siglec-F in vivo in mice may not provide identical mechanistic predictions for consequences of Siglec-8 targeting in vivo in humans.en_US
dc.description.sponsorshipJH Libraries Open Access Funden_US
dc.identifier.citationdoi: 10.1371/journal.pone.0068143en_US
dc.identifier.issn1932-6203
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/36737
dc.language.isoen_USen_US
dc.publisherPLoS Organizationen_US
dc.relation.ispartofseriesPLoS ONE;v. 8 no. 6 p. e68143
dc.subjectApoptosisen_US
dc.subjectBlooden_US
dc.subjectCell deathen_US
dc.subjectEosinophilsen_US
dc.subjectKinase inhibitorsen_US
dc.subjectMitochondriaen_US
dc.subjectMouse modelsen_US
dc.subjectSpleenen_US
dc.titleMechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.en_US
dc.typeArticleen_US
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