Radical-containing particles activate dendritic cells and enhance Th17 inflammation in a mouse model of asthma

Pingli Wang, Paul Thevenot, Jordy Saravia, Terry Ahlert, Stephania Cormier

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

We identified a previously unrecognized component of airborne particulate matter (PM) formed in combustion and thermal processes, namely, environmentally persistent free radicals (EPFRs). The pulmonary health effects of EPFRs are currently unknown. In the present study, we used a model EPFR-containing pollutant-particle system referred to as MCP230. We evaluated the effects of MCP230 on the phenotype and function of bone marrow - derived dendritic cells (BMDCs) in vitro and lung dendritic cells (DCs) in vivo, and the subsequent T-cell response. We also investigated the adjuvant role of MCP230 on airway inflammation in a mouse model of asthma. MCP230 decreased intracellular reduced glutathione (GSH) and the GSH/oxidized glutathione ratio in BMDCs, and up-regulated the expression of costimulatory molecules CD80 and CD86 on DCs. The maturation of DCs was blocked by inhibiting oxidative stress or the uptake of MCP230. BMDCs exposed to MCP230 increased their antigen-specific T-cell proliferation in vitro. In a model of asthma, exposure to MCP230 exacerbated pulmonary inflammation, which was attributed to the increase of neutrophils and macrophages but not eosinophils. This result correlated with an increase in Th17 cells and cytokines, compared with non - MCP230-treated but ovalbumin (OVA) - challenged mice. The percentage of Th2 cells was comparable between OVA and OVA + MCP230 mice. Our data demonstrate that combustion-generated, EPFR-containing PM directly induced the maturation of DCs in an uptake-dependent and oxidative stress - dependent manner. Furthermore, EPFR-containing PM induced a Th17-biased phenotype in lung, accompanied by significant pulmonary neutrophilia. Exposure to EPFR-containing PM may constitute an important and unrecognized risk factor in the exacerbation and development of a severe asthma phenotype in humans.

Original languageEnglish (US)
Pages (from-to)977-983
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number5
DOIs
StatePublished - Nov 1 2011

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Dendritic Cells
Asthma
Free Radicals
Inflammation
Particulate Matter
Ovalbumin
Lung
Bone
Oxidative stress
T-cells
Bone Marrow
Phenotype
Oxidative Stress
T-Lymphocytes
Th17 Cells
Th2 Cells
Glutathione Disulfide
Macrophages
Cell proliferation
Eosinophils

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

Cite this

Radical-containing particles activate dendritic cells and enhance Th17 inflammation in a mouse model of asthma. / Wang, Pingli; Thevenot, Paul; Saravia, Jordy; Ahlert, Terry; Cormier, Stephania.

In: American journal of respiratory cell and molecular biology, Vol. 45, No. 5, 01.11.2011, p. 977-983.

Research output: Contribution to journalArticle

Wang, Pingli ; Thevenot, Paul ; Saravia, Jordy ; Ahlert, Terry ; Cormier, Stephania. / Radical-containing particles activate dendritic cells and enhance Th17 inflammation in a mouse model of asthma. In: American journal of respiratory cell and molecular biology. 2011 ; Vol. 45, No. 5. pp. 977-983.
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