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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...

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Autores principales: Hsu, Hsiang-Ting, Mace, Emily M., Carisey, Alexandre F., Viswanath, Dixita I., Christakou, Athanasia E., Wiklund, Martin, Önfelt, Björn, Orange, Jordan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2016
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.
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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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