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

<h4>Background</h4>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 lit...

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Autores principales:	Hui Mao, Gen Kano, Sherry A Hudson, Mary Brummet, Nives Zimmermann, Zhou Zhu, Bruce S Bochner
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b7f42af47e8453a94266e3db410344e
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spelling	oai:doaj.org-article:4b7f42af47e8453a94266e3db410344e2021-11-18T07:39:20ZMechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.1932-620310.1371/journal.pone.0068143https://doaj.org/article/4b7f42af47e8453a94266e3db410344e2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23840825/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Hui MaoGen KanoSherry A HudsonMary BrummetNives ZimmermannZhou ZhuBruce S BochnerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e68143 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hui Mao Gen Kano Sherry A Hudson Mary Brummet Nives Zimmermann Zhou Zhu Bruce S Bochner Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.
description	<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
format	article
author	Hui Mao Gen Kano Sherry A Hudson Mary Brummet Nives Zimmermann Zhou Zhu Bruce S Bochner
author_facet	Hui Mao Gen Kano Sherry A Hudson Mary Brummet Nives Zimmermann Zhou Zhu Bruce S Bochner
author_sort	Hui Mao
title	Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.
title_short	Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.
title_full	Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.
title_fullStr	Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.
title_full_unstemmed	Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.
title_sort	mechanisms of siglec-f-induced eosinophil apoptosis: a role for caspases but not for shp-1, src kinases, nadph oxidase or reactive oxygen.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/4b7f42af47e8453a94266e3db410344e
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Mechanisms of Siglec-F-induced eosinophil apoptosis: a role for caspases but not for SHP-1, Src kinases, NADPH oxidase or reactive oxygen.

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