title: Pulmonary T cell activation in response to chronic particulate air pollution.
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.
authors.affiliation: Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Deiuliis
authors.forename: Thomas
authors.initials: T
authors.lastname: Kampfrath
authors.forename: Jixin
authors.initials: J
authors.lastname: Zhong
authors.forename: Steve
authors.initials: S
authors.lastname: Oghumu
authors.forename: Andrei
authors.initials: A
authors.lastname: Maiseyeu
authors.forename: Lung Chi
authors.initials: LC
authors.lastname: Chen
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.forename: Abhay R
authors.initials: AR
authors.lastname: Satoskar
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
mesh_terms: D056704:Adaptive Immunity; D000397:Air Pollution; D000818:Animals; D002452:Cell Count; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D052638:Particulate Matter / Q000276:immunology / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D054367:Receptors, CXCR3 / Q000172:deficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory
chemical_list: C515188:Cxcr3 protein, mouse; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D052638:Particulate Matter; D010743:Phospholipids; D054367:Receptors, CXCR3