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Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism

Neutrophils constitute the largest class of white blood cells and are the first responders in the innate immune response. They are able to sense and migrate up concentration gradients of chemoattractants in search of primary sites of infection and inflammation through a process known as chemotaxis....

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Autores principales: Byrne, Matthew B., Kimura, Yuki, Kapoor, Ashish, He, Yuan, Mattam, Kewin S., Hasan, Katherine M., Olson, Luke N., Wang, Fei, Kenis, Paul J. A., Rao, Christopher V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897492/
https://www.ncbi.nlm.nih.gov/pubmed/24465668
http://dx.doi.org/10.1371/journal.pone.0085726
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author Byrne, Matthew B.
Kimura, Yuki
Kapoor, Ashish
He, Yuan
Mattam, Kewin S.
Hasan, Katherine M.
Olson, Luke N.
Wang, Fei
Kenis, Paul J. A.
Rao, Christopher V.
author_facet Byrne, Matthew B.
Kimura, Yuki
Kapoor, Ashish
He, Yuan
Mattam, Kewin S.
Hasan, Katherine M.
Olson, Luke N.
Wang, Fei
Kenis, Paul J. A.
Rao, Christopher V.
author_sort Byrne, Matthew B.
collection PubMed
description Neutrophils constitute the largest class of white blood cells and are the first responders in the innate immune response. They are able to sense and migrate up concentration gradients of chemoattractants in search of primary sites of infection and inflammation through a process known as chemotaxis. These chemoattractants include formylated peptides and various chemokines. While much is known about chemotaxis to individual chemoattractants, far less is known about chemotaxis towards many. Previous studies have shown that in opposing gradients of intermediate chemoattractants (interleukin-8 and leukotriene B(4)), neutrophils preferentially migrate toward the more distant source. In this work, we investigated neutrophil chemotaxis in opposing gradients of chemoattractants using a microfluidic platform. We found that primary neutrophils exhibit oscillatory motion in opposing gradients of intermediate chemoattractants. To understand this behavior, we constructed a mathematical model of neutrophil chemotaxis. Our results suggest that sensory adaptation alone cannot explain the observed oscillatory motion. Rather, our model suggests that neutrophils employ a winner-take-all mechanism that enables them to transiently lock onto sensed targets and continuously switch between the intermediate attractant sources as they are encountered. These findings uncover a previously unseen behavior of neutrophils in opposing gradients of chemoattractants that will further aid in our understanding of neutrophil chemotaxis and the innate immune response. In addition, we propose a winner-take-all mechanism allows the cells to avoid stagnation near local chemical maxima when migrating through a network of chemoattractant sources.
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spelling pubmed-38974922014-01-24 Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism Byrne, Matthew B. Kimura, Yuki Kapoor, Ashish He, Yuan Mattam, Kewin S. Hasan, Katherine M. Olson, Luke N. Wang, Fei Kenis, Paul J. A. Rao, Christopher V. PLoS One Research Article Neutrophils constitute the largest class of white blood cells and are the first responders in the innate immune response. They are able to sense and migrate up concentration gradients of chemoattractants in search of primary sites of infection and inflammation through a process known as chemotaxis. These chemoattractants include formylated peptides and various chemokines. While much is known about chemotaxis to individual chemoattractants, far less is known about chemotaxis towards many. Previous studies have shown that in opposing gradients of intermediate chemoattractants (interleukin-8 and leukotriene B(4)), neutrophils preferentially migrate toward the more distant source. In this work, we investigated neutrophil chemotaxis in opposing gradients of chemoattractants using a microfluidic platform. We found that primary neutrophils exhibit oscillatory motion in opposing gradients of intermediate chemoattractants. To understand this behavior, we constructed a mathematical model of neutrophil chemotaxis. Our results suggest that sensory adaptation alone cannot explain the observed oscillatory motion. Rather, our model suggests that neutrophils employ a winner-take-all mechanism that enables them to transiently lock onto sensed targets and continuously switch between the intermediate attractant sources as they are encountered. These findings uncover a previously unseen behavior of neutrophils in opposing gradients of chemoattractants that will further aid in our understanding of neutrophil chemotaxis and the innate immune response. In addition, we propose a winner-take-all mechanism allows the cells to avoid stagnation near local chemical maxima when migrating through a network of chemoattractant sources. Public Library of Science 2014-01-21 /pmc/articles/PMC3897492/ /pubmed/24465668 http://dx.doi.org/10.1371/journal.pone.0085726 Text en © 2014 Byrne et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Byrne, Matthew B.
Kimura, Yuki
Kapoor, Ashish
He, Yuan
Mattam, Kewin S.
Hasan, Katherine M.
Olson, Luke N.
Wang, Fei
Kenis, Paul J. A.
Rao, Christopher V.
Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism
title Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism
title_full Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism
title_fullStr Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism
title_full_unstemmed Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism
title_short Oscillatory Behavior of Neutrophils under Opposing Chemoattractant Gradients Supports a Winner-Take-All Mechanism
title_sort oscillatory behavior of neutrophils under opposing chemoattractant gradients supports a winner-take-all mechanism
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897492/
https://www.ncbi.nlm.nih.gov/pubmed/24465668
http://dx.doi.org/10.1371/journal.pone.0085726
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