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Nox2 Is Required for Macrophage Chemotaxis towards CSF-1

Macrophage migration and infiltration is an important first step in many pathophysiological processes, in particular inflammatory diseases. Redox modulation of the migratory signalling processes has been reported in endothelial cells, vascular smooth muscle cells and fibroblasts. However the redox m...

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Autores principales: Chaubey, Sanjay, Jones, Gareth E., Shah, Ajay M., Cave, Alison C., Wells, Claire M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562318/
https://www.ncbi.nlm.nih.gov/pubmed/23383302
http://dx.doi.org/10.1371/journal.pone.0054869
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author Chaubey, Sanjay
Jones, Gareth E.
Shah, Ajay M.
Cave, Alison C.
Wells, Claire M.
author_facet Chaubey, Sanjay
Jones, Gareth E.
Shah, Ajay M.
Cave, Alison C.
Wells, Claire M.
author_sort Chaubey, Sanjay
collection PubMed
description Macrophage migration and infiltration is an important first step in many pathophysiological processes, in particular inflammatory diseases. Redox modulation of the migratory signalling processes has been reported in endothelial cells, vascular smooth muscle cells and fibroblasts. However the redox modulation of the migratory process in macrophages and in particular that from the NADPH oxidase-2 (Nox2) dependent ROS has not been established. To investigate the potential role of Nox2 in the migratory response of macrophages, bone marrow derived macrophages were obtained from WT and NOX2 knockout mice (Nox2KO) and subjected to CSF-1 stimulation. We report here that loss of Nox2 expression in BMM resulted in a significant reduction in the CSF-1 induced spreading response suggesting that Nox2 can modulate cytoskeletal events. Moreover, Nox2KO BMMs were deficient in cellular displacement in the presence of CSF-1. More significantly, when challenged with a gradient of CSF-1, Nox2KO BMMs showed a complete loss of chemotaxis accompanied by a reduction in cell migration speed and directional migration persistence. These results point to a specific role for Nox2KO downstream of CSF-1 during the BMM migratory response. Indeed, we have further found that Nox2KO BMMs display a significant reduction in the levels of ERK1/2 phosphorylation following stimulation with CSF-1.Thus Nox2 is important in BMM cellular motion to CSF-1 stimulation and necessary for their directed migration towards a CSF-1 gradient, highlighting Nox2 dependent signalling as a potential anti-inflammatory target.
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spelling pubmed-35623182013-02-04 Nox2 Is Required for Macrophage Chemotaxis towards CSF-1 Chaubey, Sanjay Jones, Gareth E. Shah, Ajay M. Cave, Alison C. Wells, Claire M. PLoS One Research Article Macrophage migration and infiltration is an important first step in many pathophysiological processes, in particular inflammatory diseases. Redox modulation of the migratory signalling processes has been reported in endothelial cells, vascular smooth muscle cells and fibroblasts. However the redox modulation of the migratory process in macrophages and in particular that from the NADPH oxidase-2 (Nox2) dependent ROS has not been established. To investigate the potential role of Nox2 in the migratory response of macrophages, bone marrow derived macrophages were obtained from WT and NOX2 knockout mice (Nox2KO) and subjected to CSF-1 stimulation. We report here that loss of Nox2 expression in BMM resulted in a significant reduction in the CSF-1 induced spreading response suggesting that Nox2 can modulate cytoskeletal events. Moreover, Nox2KO BMMs were deficient in cellular displacement in the presence of CSF-1. More significantly, when challenged with a gradient of CSF-1, Nox2KO BMMs showed a complete loss of chemotaxis accompanied by a reduction in cell migration speed and directional migration persistence. These results point to a specific role for Nox2KO downstream of CSF-1 during the BMM migratory response. Indeed, we have further found that Nox2KO BMMs display a significant reduction in the levels of ERK1/2 phosphorylation following stimulation with CSF-1.Thus Nox2 is important in BMM cellular motion to CSF-1 stimulation and necessary for their directed migration towards a CSF-1 gradient, highlighting Nox2 dependent signalling as a potential anti-inflammatory target. Public Library of Science 2013-02-01 /pmc/articles/PMC3562318/ /pubmed/23383302 http://dx.doi.org/10.1371/journal.pone.0054869 Text en © 2013 Chaubey 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
Chaubey, Sanjay
Jones, Gareth E.
Shah, Ajay M.
Cave, Alison C.
Wells, Claire M.
Nox2 Is Required for Macrophage Chemotaxis towards CSF-1
title Nox2 Is Required for Macrophage Chemotaxis towards CSF-1
title_full Nox2 Is Required for Macrophage Chemotaxis towards CSF-1
title_fullStr Nox2 Is Required for Macrophage Chemotaxis towards CSF-1
title_full_unstemmed Nox2 Is Required for Macrophage Chemotaxis towards CSF-1
title_short Nox2 Is Required for Macrophage Chemotaxis towards CSF-1
title_sort nox2 is required for macrophage chemotaxis towards csf-1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3562318/
https://www.ncbi.nlm.nih.gov/pubmed/23383302
http://dx.doi.org/10.1371/journal.pone.0054869
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