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Pulmonary T cell activation in response to chronic particulate air pollution

Am J Physiol Lung Cell Mol Physiol. 2012 Feb 15;302(4):L399-409. doi: 10.1152/ajplung.00261.2011. Epub 2011 Dec 9.

Abstract

The purpose of this study was to investigate the effects of chronically inhaled particulate matter <2.5 μm (PM(2.5)) on inflammatory cell populations in the lung and systemic circulation. A prominent component of air pollution exposure is a systemic inflammatory response that may exaggerate chronic diseases such as atherosclerosis and insulin resistance. T cell response was measured in wild-type C57B/L6, Foxp3-green fluorescent protein (GFP) "knockin," and chemokine receptor 3 knockout (CXCR3(-/-)) mice following 24-28 wk of PM(2.5) or filtered air. Chronic PM(2.5) exposure resulted in increased CXCR3-expressing CD4(+) and CD8(+) T cells in the lungs, spleen, and blood with elevation in CD11c(+) macrophages in the lung and oxidized derivatives of 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine in wild-type mice. CXCR3 deficiency decreased T cells in the lung. GFP(+) regulatory T cells increased with PM(2.5) exposure in the spleen and blood of Foxp3-GFP mice but were present at very low levels in the lung irrespective of PM(2.5) exposure. Mixed lymphocyte cultures using primary, PM(2.5)-treated macrophages demonstrated enhanced T cell proliferation. Our experiments indicate that PM(2.5) potentiates a proinflammatory Th1 response involving increased homing of CXCR3(+) T effector cells to the lung and modulation of systemic T cell populations.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Air Pollution*
  • Animals
  • Cell Count
  • Cell Proliferation
  • Cells, Cultured
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Gene Expression
  • Immunity, Innate
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Lymph Nodes / pathology
  • Lymphocyte Activation*
  • Macrophage Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidation-Reduction
  • Particulate Matter / immunology
  • Particulate Matter / toxicity*
  • Phospholipids / metabolism
  • Promoter Regions, Genetic
  • Receptors, CXCR3 / deficiency
  • Receptors, CXCR3 / genetics
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory

Substances

  • Cxcr3 protein, mouse
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Il17a protein, mouse
  • Interleukin-17
  • Particulate Matter
  • Phospholipids
  • Receptors, CXCR3