Regulation of Monocyte Adhesion and Migration by Nox4

Chi Fung Lee, Sarah Ullevig, Hong Seok Kim, Reto Asmis

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We showed that metabolic disorders promote thiol oxidative stress in monocytes, priming monocytes for accelerated chemokine-induced recruitment, and accumulation at sites of vascular injury and the progression of atherosclerosis. The aim of this study was to identify both the source of reactive oxygen species (ROS) responsible for thiol oxidation in primed and dysfunctional monocytes and the molecular mechanisms through which ROS accelerate the migration and recruitment of monocyte-derived macrophages. We found that Nox4, a recently identified NADPH oxidase in monocytes and macrophages, localized to focal adhesions and the actin cytoskeleton, and associated with phospho-FAK, paxillin, and actin, implicating Nox4 in the regulation of monocyte adhesion and migration. We also identified Nox4 as a new, metabolic stress-inducible source of ROS that controls actin S-glutathionylation and turnover in monocytes and macrophages, providing a novel mechanistic link between Nox4-derived H2O2 and monocyte adhesion and migration. Actin associated with Nox4 was S-glutathionylated, and Nox4 association with actin was enhanced in metabolically-stressed monocytes. Metabolic stress induced Nox4 and accelerated monocyte adhesion and chemotaxis in a Nox4-dependent mechanism. In conclusion, our data suggest that monocytic Nox4 is a central regulator of actin dynamics, and induction of Nox4 is the rate-limiting step in metabolic stress-induced monocyte priming and dysfunction associated with accelerated atherosclerosis and the progression of atherosclerotic plaques.

Original languageEnglish (US)
Article numbere66964
JournalPLoS One
Volume8
Issue number6
DOIs
StatePublished - Jun 18 2013

Fingerprint

monocytes
adhesion
Actins
Monocytes
Adhesion
Macrophages
Reactive Oxygen Species
actin
Physiological Stress
Sulfhydryl Compounds
reactive oxygen species
Paxillin
macrophages
Oxidative stress
NADPH Oxidase
atherosclerosis
thiols
Atherosclerosis
Chemokines
Association reactions

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lee, C. F., Ullevig, S., Kim, H. S., & Asmis, R. (2013). Regulation of Monocyte Adhesion and Migration by Nox4. PLoS One, 8(6), [e66964]. https://doi.org/10.1371/journal.pone.0066964

Regulation of Monocyte Adhesion and Migration by Nox4. / Lee, Chi Fung; Ullevig, Sarah; Kim, Hong Seok; Asmis, Reto.

In: PLoS One, Vol. 8, No. 6, e66964, 18.06.2013.

Research output: Contribution to journalArticle

Lee, CF, Ullevig, S, Kim, HS & Asmis, R 2013, 'Regulation of Monocyte Adhesion and Migration by Nox4', PLoS One, vol. 8, no. 6, e66964. https://doi.org/10.1371/journal.pone.0066964
Lee, Chi Fung ; Ullevig, Sarah ; Kim, Hong Seok ; Asmis, Reto. / Regulation of Monocyte Adhesion and Migration by Nox4. In: PLoS One. 2013 ; Vol. 8, No. 6.
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