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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Main Authors: Sanjay Chaubey, Gareth E Jones, Ajay M Shah, Alison C Cave, Claire M Wells
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054869&type=printable
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author Sanjay Chaubey
Gareth E Jones
Ajay M Shah
Alison C Cave
Claire M Wells
author_facet Sanjay Chaubey
Gareth E Jones
Ajay M Shah
Alison C Cave
Claire M Wells
author_sort Sanjay Chaubey
collection DOAJ
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 doaj-art-2fdd4d7494164980b221c6324bde683b2025-08-20T03:09:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5486910.1371/journal.pone.0054869Nox2 is required for macrophage chemotaxis towards CSF-1.Sanjay ChaubeyGareth E JonesAjay M ShahAlison C CaveClaire M WellsMacrophage 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054869&type=printable
spellingShingle Sanjay Chaubey
Gareth E Jones
Ajay M Shah
Alison C Cave
Claire M Wells
Nox2 is required for macrophage chemotaxis towards CSF-1.
PLoS ONE
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
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0054869&type=printable
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