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Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay

Migrating cells often exhibit signal relay, a process in which cells migrating in response to a chemotactic gradient release a secondary chemoattractant to enhance directional migration. In neutrophils, signal relay toward the primary chemoattractant N-­formylmethionyl-leucyl-phenylalanine (fMLP) is...

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Autores principales: Szatmary, Alex C., Nossal, Ralph, Parent, Carole A., Majumdar, Ritankar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687044/
https://www.ncbi.nlm.nih.gov/pubmed/28954858
http://dx.doi.org/10.1091/mbc.E17-05-0298
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author Szatmary, Alex C.
Nossal, Ralph
Parent, Carole A.
Majumdar, Ritankar
author_facet Szatmary, Alex C.
Nossal, Ralph
Parent, Carole A.
Majumdar, Ritankar
author_sort Szatmary, Alex C.
collection PubMed
description Migrating cells often exhibit signal relay, a process in which cells migrating in response to a chemotactic gradient release a secondary chemoattractant to enhance directional migration. In neutrophils, signal relay toward the primary chemoattractant N-­formylmethionyl-leucyl-phenylalanine (fMLP) is mediated by leukotriene B(4) (LTB(4)). Recent evidence suggests that the release of LTB(4) from cells occurs through packaging in exosomes. Here we present a mathematical model of neutrophil signal relay that focuses on LTB(4) and its exosome-mediated secretion. We describe neutrophil chemotaxis in response to a combination of a defined gradient of fMLP and an evolving gradient of LTB(4), generated by cells in response to fMLP. Our model enables us to determine the gradient of LTB(4) arising either through directed secretion from cells or through time-varying release from exosomes. We predict that the secondary release of LTB(4) increases recruitment range and show that the exosomes provide a time delay mechanism that regulates the development of LTB(4) gradients. Additionally, we show that under decaying primary gradients, secondary gradients are more stable when secreted through exosomes as compared with direct secretion. Our chemotactic model, calibrated from observed responses of cells to gradients, thereby provides insight into chemotactic signal relay in neutrophils during inflammation.
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spelling pubmed-56870442018-01-22 Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay Szatmary, Alex C. Nossal, Ralph Parent, Carole A. Majumdar, Ritankar Mol Biol Cell Articles Migrating cells often exhibit signal relay, a process in which cells migrating in response to a chemotactic gradient release a secondary chemoattractant to enhance directional migration. In neutrophils, signal relay toward the primary chemoattractant N-­formylmethionyl-leucyl-phenylalanine (fMLP) is mediated by leukotriene B(4) (LTB(4)). Recent evidence suggests that the release of LTB(4) from cells occurs through packaging in exosomes. Here we present a mathematical model of neutrophil signal relay that focuses on LTB(4) and its exosome-mediated secretion. We describe neutrophil chemotaxis in response to a combination of a defined gradient of fMLP and an evolving gradient of LTB(4), generated by cells in response to fMLP. Our model enables us to determine the gradient of LTB(4) arising either through directed secretion from cells or through time-varying release from exosomes. We predict that the secondary release of LTB(4) increases recruitment range and show that the exosomes provide a time delay mechanism that regulates the development of LTB(4) gradients. Additionally, we show that under decaying primary gradients, secondary gradients are more stable when secreted through exosomes as compared with direct secretion. Our chemotactic model, calibrated from observed responses of cells to gradients, thereby provides insight into chemotactic signal relay in neutrophils during inflammation. The American Society for Cell Biology 2017-11-07 /pmc/articles/PMC5687044/ /pubmed/28954858 http://dx.doi.org/10.1091/mbc.E17-05-0298 Text en © 2017 Szatmary et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Szatmary, Alex C.
Nossal, Ralph
Parent, Carole A.
Majumdar, Ritankar
Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay
title Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay
title_full Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay
title_fullStr Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay
title_full_unstemmed Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay
title_short Modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay
title_sort modeling neutrophil migration in dynamic chemoattractant gradients: assessing the role of exosomes during signal relay
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687044/
https://www.ncbi.nlm.nih.gov/pubmed/28954858
http://dx.doi.org/10.1091/mbc.E17-05-0298
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