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NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing
Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein- and integrin signal–dependent movement of lysosome-related organelles to the microtubule-organizing center, as an early step...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166499/ https://www.ncbi.nlm.nih.gov/pubmed/27903610 http://dx.doi.org/10.1083/jcb.201604136 |
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author | Hsu, Hsiang-Ting Mace, Emily M. Carisey, Alexandre F. Viswanath, Dixita I. Christakou, Athanasia E. Wiklund, Martin Önfelt, Björn Orange, Jordan S. |
author_facet | Hsu, Hsiang-Ting Mace, Emily M. Carisey, Alexandre F. Viswanath, Dixita I. Christakou, Athanasia E. Wiklund, Martin Önfelt, Björn Orange, Jordan S. |
author_sort | Hsu, Hsiang-Ting |
collection | PubMed |
description | Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein- and integrin signal–dependent movement of lysosome-related organelles to the microtubule-organizing center, as an early step in the cell biological process underlying NK cell cytotoxicity. Why lytic granules converge during NK cell cytotoxicity, however, remains unclear. We experimentally controlled the availability of human ligands to regulate NK cell signaling and promote granule convergence with either directed or nondirected degranulation. By the use of acoustic trap microscopy, we generated specific effector–target cell arrangements to define the impact of the two modes of degranulation. NK cells with converged granules had greater targeted and less nonspecific “bystander” killing. Additionally, NK cells in which dynein was inhibited or integrin blocked under physiological conditions demonstrated increased nondirected degranulation and bystander killing. Thus, NK cells converge lytic granules and thereby improve the efficiency of targeted killing and prevent collateral damage to neighboring healthy cells. |
format | Online Article Text |
id | pubmed-5166499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51664992017-06-19 NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing Hsu, Hsiang-Ting Mace, Emily M. Carisey, Alexandre F. Viswanath, Dixita I. Christakou, Athanasia E. Wiklund, Martin Önfelt, Björn Orange, Jordan S. J Cell Biol Research Articles Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein- and integrin signal–dependent movement of lysosome-related organelles to the microtubule-organizing center, as an early step in the cell biological process underlying NK cell cytotoxicity. Why lytic granules converge during NK cell cytotoxicity, however, remains unclear. We experimentally controlled the availability of human ligands to regulate NK cell signaling and promote granule convergence with either directed or nondirected degranulation. By the use of acoustic trap microscopy, we generated specific effector–target cell arrangements to define the impact of the two modes of degranulation. NK cells with converged granules had greater targeted and less nonspecific “bystander” killing. Additionally, NK cells in which dynein was inhibited or integrin blocked under physiological conditions demonstrated increased nondirected degranulation and bystander killing. Thus, NK cells converge lytic granules and thereby improve the efficiency of targeted killing and prevent collateral damage to neighboring healthy cells. The Rockefeller University Press 2016-12-19 /pmc/articles/PMC5166499/ /pubmed/27903610 http://dx.doi.org/10.1083/jcb.201604136 Text en © 2016 Hsu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Hsu, Hsiang-Ting Mace, Emily M. Carisey, Alexandre F. Viswanath, Dixita I. Christakou, Athanasia E. Wiklund, Martin Önfelt, Björn Orange, Jordan S. NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing |
title | NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing |
title_full | NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing |
title_fullStr | NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing |
title_full_unstemmed | NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing |
title_short | NK cells converge lytic granules to promote cytotoxicity and prevent bystander killing |
title_sort | nk cells converge lytic granules to promote cytotoxicity and prevent bystander killing |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166499/ https://www.ncbi.nlm.nih.gov/pubmed/27903610 http://dx.doi.org/10.1083/jcb.201604136 |
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