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Table of Contents
Vol. 3, No. 2, 2011
Issue release date: February 2011
Section title: Research Article
Free Access
J Innate Immun 2011;3:150–166
(DOI:10.1159/000321725)

Activation of Pulmonary Dendritic Cells and Th2-Type Inflammatory Responses on Instillation of Engineered, Environmental Diesel Emission Source or Ambient Air Pollutant Particles in vivo

Bezemer G.F.G.a · Bauer S.M.b · Oberdörster G.c, e · Breysse P.N.f · Pieters R.H.H.a · Georas S.N.b, d, e · Williams M.A.b, d, e
aImmunotoxicology Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands; bDivision of Pulmonary and Critical Care Medicine, cDivision of Respiratory Biology and Toxicology, dLung Biology and Disease Program, eDepartment of Environmental Medicine, University of Rochester School of Medicine and Dentistry, Rochester, N.Y., and fDepartment of Environmental Health Sciences, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Md., USA
email Corresponding Author

Abstract

The biological effects of acute particulate air pollution exposure in host innate immunity remain obscure and have relied largely on in vitro models. We hypothesized that single acute exposure to ambient or engineered particulate matter (PM) in the absence of other secondary stimuli would activate lung dendritic cells (DC) in vivo and provide information on the early immunological events of PM exposure and DC activation in a mouse model naïve to prior PM exposure. Activation of purified lung DC was studied following oropharyngeal instillation of ambient particulate matter (APM). We compared the effects of APM exposure with that of diesel-enriched PM (DEP), carbon black particles (CBP) and silver nanoparticles (AgP). We found that PM species induced variable cellular infiltration in the lungs and only APM exposure induced eosinophilic infiltration. Both APM and DEP activated pulmonary DC and promoted a Th2-type cytokine response from naïve CD4+ T cells ex vivo. Cultures of primary peribronchial lymph node cells from mice exposed to APM and DEP also displayed a Th2-type immune response ex vivo. We conclude that exposure of the lower airway to various PM species induces differential immunological responses and immunomodulation of DC subsets. Environmental APM and DEP activated DC in vivo and provoked a Th2 response ex vivo. By contrast, CBP and AgP induced altered lung tissue barrier integrity but failed to stimulate CD4+ T cells as effectively. Our work suggests that respirable pollutants activate the innate immune response with enhanced DC activation, pulmonary inflammation and Th2-immune responsiveness.

© 2010 S. Karger AG, Basel


  

Key Words

  • Innate immunity
  • Allergic immunity
  • Dendritic cell
  • Lung
  • Inflammation
  • Immunotoxicology
  • Toxicology
  • Particulate matter
  • Nanoparticles

References

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  3. Nel AE, Diaz-Sanchez D, Ng D, Hiura T, Saxon A: Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system. J Allergy Clin Immunol 2008;102:539–554.
  4. Wills-Karp M: Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 1999;17:255–281.
  5. Porter M, Karp M, Killedar S, Bauer SM, Guo J, Williams D, Breysse P, Georas SN, Williams MA: Diesel-enriched particulate matter functionally activates human dendritic cells. Am J Respir Cell Mol Biol 2007;37:706–719.
  6. Williams MA, Porter M, Horton M, Guo J, Roman J, Williams D, Breysse P, Georas SN: Ambient particulate matter directs nonclassic dendritic cell activation and a mixed T(H)1/T(H)2-like cytokine response by naive CD4(+) T cells. J Allergy Clin Immunol 2007;119:488–497.
  7. Miyabara Y, Ichinose T, Takano H, Lim HB, Sagai M: Effects of diesel exhaust on allergic airway inflammation in mice. J Allergy Clin Immunol 1998;102:805–812.
  8. Granum B, Løvik M: The effect of particles on allergic immune responses. Toxicol Sci 2002;65:7–17.
  9. Mamessier E, Nieves A, Vervloet D, Magnan A: Diesel exhaust particles enhance T-cell activation in severe asthmatics. Allergy 2006;61:581–588.
  10. Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutch WA: Role of free radicals in the toxicity of airborne fine particulate matter. Chem Res Toxicol 2001;14:1371–1377.
  11. Baulig A, Singh S, Marchand A, Schins R, Barouki R, Garlatti M, Marano F, Baeza-Squiban A: Role of Paris PM(2.5) components in the pro-inflammatory response induced in airway epithelial cells. Toxicology 2009;261:126–135.
  12. Williams MA, Rangasamy T, Bauer SM, Killedar S, Karp M, Kensler TW, Yamamoto M, Breysse P, Biswal S, Georas SN: Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. J Immunol 2008;181:4545–4559.
  13. Kadiiska MB, Mason RP, Dreher KL, Costa DL, Ghio AJ: In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. Chem Res Toxicol 2007;10:1104–1108.

    External Resources

  14. Becker S, Dailey LA, Soukup JM, Grambow SC, Devlin RB, Huang YC: Seasonal variations in air pollution particle-induced inflammatory mediator release and oxidative stress. Environ Health Perspect 2005;113:1032–1038.
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  18. Rangasamy T, Williams MA, Bauer S, Trush MA, Emo J, Georas SN, Biswal S: Nrf2 inhibits the maturation of murine dendritic cells by ragweed extract. Am J Respir Cell Mol Biol 2010;43:276–285.
  19. Williams MA, Cheadle C, Watkins T, Tailor A, Killedar SY, Breysse P, Barnes K, Georas SN: TLR2 and TLR4 as potential biomarkers of environmental particulate matter exposed human myeloid dendritic cells. Biomarker Insights 2007;2:225–239.
  20. Hammad HM, Kool M, Lambrecht BN: Role of airway dendritic cell subsets in asthma. Cytometry B Clin Cytom 2007;72B:120–121.

    External Resources

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  28. de Haar C, Hassing I, Bol M, Bleumink R, Pieters R: Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model. Toxicol Sci 2005;87:409–418.
  29. de Haar C, Hassing I, Bol M, Bleumink R, Pieters R: Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice. Clin Exp Allergy 2006;36:1469–1479.
  30. de Haar C, Kool M, Hassing I, Bol M, Lambrecht BN, Pieters R: Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity. J Allergy Clin Immunol 2008;121:1246–1254.
  31. de Heer HJ, Hammad H, Soullié T, Hijdra D, Vos N, Willart MA, Hoogsteden HC, Lambrecht BN: Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 2004;200:89–98.
  32. Ohtani T, Nakagawa S, Kurosawa M, Mizuashi M, Ozawa M, Aiba S: Cellular basis of the role of diesel exhaust particles in inducing Th2-dominant response. J Immunol 2005;174:2412–2419.
  33. van Rijt LS, Jung S, Kleinjan A, Vos N, Willart M, Duez C, Hoogsteden HC, Lambrecht BN: In vivo depletion of lung CD11c (+) dendritic cells during allergen challenge abrogates the characteristic features of asthma. J Exp Med 2005;201:981–991.
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  49. Ng N, Lam D, Paulus P, Batzer G, Horner AA: House dust extracts have both Th2 adjuvant and tolerogenic activities. J Allergy Clin Immunol 2006;117:1074–1081.
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Author Contacts

Dr. Marc Adrian Williams
NHEERL, Environmental Public Health Division, Cardiopulmonary and Immunotoxicology Branch, Office of Research and Development
US Environmental Protection Agency, Research Triangle Park, NC 27711 (USA)
Tel. +1 919 541 2255, E-Mail Williams.marc@epa.gov

  

Article Information

Received: August 16, 2010
Accepted after revision: October 6, 2010
Published online: November 23, 2010
Number of Print Pages : 17
Number of Figures : 7, Number of Tables : 1, Number of References : 65

  

Publication Details

Journal of Innate Immunity

Vol. 3, No. 2, Year 2011 (Cover Date: February 2011)

Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

The biological effects of acute particulate air pollution exposure in host innate immunity remain obscure and have relied largely on in vitro models. We hypothesized that single acute exposure to ambient or engineered particulate matter (PM) in the absence of other secondary stimuli would activate lung dendritic cells (DC) in vivo and provide information on the early immunological events of PM exposure and DC activation in a mouse model naïve to prior PM exposure. Activation of purified lung DC was studied following oropharyngeal instillation of ambient particulate matter (APM). We compared the effects of APM exposure with that of diesel-enriched PM (DEP), carbon black particles (CBP) and silver nanoparticles (AgP). We found that PM species induced variable cellular infiltration in the lungs and only APM exposure induced eosinophilic infiltration. Both APM and DEP activated pulmonary DC and promoted a Th2-type cytokine response from naïve CD4+ T cells ex vivo. Cultures of primary peribronchial lymph node cells from mice exposed to APM and DEP also displayed a Th2-type immune response ex vivo. We conclude that exposure of the lower airway to various PM species induces differential immunological responses and immunomodulation of DC subsets. Environmental APM and DEP activated DC in vivo and provoked a Th2 response ex vivo. By contrast, CBP and AgP induced altered lung tissue barrier integrity but failed to stimulate CD4+ T cells as effectively. Our work suggests that respirable pollutants activate the innate immune response with enhanced DC activation, pulmonary inflammation and Th2-immune responsiveness.

© 2010 S. Karger AG, Basel


  

Author Contacts

Dr. Marc Adrian Williams
NHEERL, Environmental Public Health Division, Cardiopulmonary and Immunotoxicology Branch, Office of Research and Development
US Environmental Protection Agency, Research Triangle Park, NC 27711 (USA)
Tel. +1 919 541 2255, E-Mail Williams.marc@epa.gov

  

Article Information

Received: August 16, 2010
Accepted after revision: October 6, 2010
Published online: November 23, 2010
Number of Print Pages : 17
Number of Figures : 7, Number of Tables : 1, Number of References : 65

  

Publication Details

Journal of Innate Immunity

Vol. 3, No. 2, Year 2011 (Cover Date: February 2011)

Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN


Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: 8/16/2010
Accepted: 10/6/2010
Published online: 11/23/2010
Issue release date: February 2011

Number of Print Pages: 17
Number of Figures: 7
Number of Tables: 1

ISSN: 1662-811X (Print)
eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Cohn L, Elias JA, Chupp GL: Asthma: mechanisms of disease persistence and progression. Annu Rev Immunol 2004;22:789–815.
  2. Galli SJ, Tsai M, Piliponsky AM: The development of allergic inflammation. Nature 2008;454:445–454.
  3. Nel AE, Diaz-Sanchez D, Ng D, Hiura T, Saxon A: Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system. J Allergy Clin Immunol 2008;102:539–554.
  4. Wills-Karp M: Immunologic basis of antigen-induced airway hyperresponsiveness. Annu Rev Immunol 1999;17:255–281.
  5. Porter M, Karp M, Killedar S, Bauer SM, Guo J, Williams D, Breysse P, Georas SN, Williams MA: Diesel-enriched particulate matter functionally activates human dendritic cells. Am J Respir Cell Mol Biol 2007;37:706–719.
  6. Williams MA, Porter M, Horton M, Guo J, Roman J, Williams D, Breysse P, Georas SN: Ambient particulate matter directs nonclassic dendritic cell activation and a mixed T(H)1/T(H)2-like cytokine response by naive CD4(+) T cells. J Allergy Clin Immunol 2007;119:488–497.
  7. Miyabara Y, Ichinose T, Takano H, Lim HB, Sagai M: Effects of diesel exhaust on allergic airway inflammation in mice. J Allergy Clin Immunol 1998;102:805–812.
  8. Granum B, Løvik M: The effect of particles on allergic immune responses. Toxicol Sci 2002;65:7–17.
  9. Mamessier E, Nieves A, Vervloet D, Magnan A: Diesel exhaust particles enhance T-cell activation in severe asthmatics. Allergy 2006;61:581–588.
  10. Dellinger B, Pryor WA, Cueto R, Squadrito GL, Hegde V, Deutch WA: Role of free radicals in the toxicity of airborne fine particulate matter. Chem Res Toxicol 2001;14:1371–1377.
  11. Baulig A, Singh S, Marchand A, Schins R, Barouki R, Garlatti M, Marano F, Baeza-Squiban A: Role of Paris PM(2.5) components in the pro-inflammatory response induced in airway epithelial cells. Toxicology 2009;261:126–135.
  12. Williams MA, Rangasamy T, Bauer SM, Killedar S, Karp M, Kensler TW, Yamamoto M, Breysse P, Biswal S, Georas SN: Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. J Immunol 2008;181:4545–4559.
  13. Kadiiska MB, Mason RP, Dreher KL, Costa DL, Ghio AJ: In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. Chem Res Toxicol 2007;10:1104–1108.

    External Resources

  14. Becker S, Dailey LA, Soukup JM, Grambow SC, Devlin RB, Huang YC: Seasonal variations in air pollution particle-induced inflammatory mediator release and oxidative stress. Environ Health Perspect 2005;113:1032–1038.
  15. Blank F, Rothen-Rutishauser B, Gehr P: Dendritic cells and macrophages form a transepithelial network against foreign particulate antigens. Am J Respir Cell Mol Biol 2007;36:669–677.
  16. Geiser M: Morphological aspects of particle uptake by lung phagocytes. Microsc Res Tech 2002;57:512–522.
  17. van Rijt LS, Lambrecht BN: Dendritic cells in asthma: a function beyond sensitization. Clin Exp Allergy 2005;35:1125–1134.
  18. Rangasamy T, Williams MA, Bauer S, Trush MA, Emo J, Georas SN, Biswal S: Nrf2 inhibits the maturation of murine dendritic cells by ragweed extract. Am J Respir Cell Mol Biol 2010;43:276–285.
  19. Williams MA, Cheadle C, Watkins T, Tailor A, Killedar SY, Breysse P, Barnes K, Georas SN: TLR2 and TLR4 as potential biomarkers of environmental particulate matter exposed human myeloid dendritic cells. Biomarker Insights 2007;2:225–239.
  20. Hammad HM, Kool M, Lambrecht BN: Role of airway dendritic cell subsets in asthma. Cytometry B Clin Cytom 2007;72B:120–121.

    External Resources

  21. Lambrecht BN, Salomon B, Klatzman D, Pauwels RA: Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J Immunol 1998;160:4090–4097.
  22. Lanckacker EA, Robays LJ, Joos GF, Vermaelen KY: A new danger in the air: how pulmonary innate immunity copes with man-made airborne xenobiotics. J Innate Immun 2010;2:96–106.
  23. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol 2000;18:767–811.
  24. Lambrecht BN, De Veerman M, Coyle AJ, Gutierrez-Ramos JC, Thielemans K, Pauwels RA: Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J Clin Invest 2000;106:551–559.
  25. Oriss TB, Ostroukhova M, Seguin-Devaux C, Dixon-McCarthy B, Stolz DB, Watkins SC, Pillemer B, Ray P, Ray A: Dynamics of dendritic cell phenotype and interactions with CD4(+) T cells in airway inflammation and tolerance. J Immunol 2005;174:854–863.
  26. Vermaelen KY, Carro-Muino I, Lambrecht BN, Pauwels RA: Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. J Exp Med 2001;193:51–60.
  27. Vermaelen K, Pauwels R: Pulmonary dendritic cells. Am J Respir Crit Care Med 2005;172:530–551.
  28. de Haar C, Hassing I, Bol M, Bleumink R, Pieters R: Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model. Toxicol Sci 2005;87:409–418.
  29. de Haar C, Hassing I, Bol M, Bleumink R, Pieters R: Ultrafine but not fine particulate matter causes airway inflammation and allergic airway sensitization to co-administered antigen in mice. Clin Exp Allergy 2006;36:1469–1479.
  30. de Haar C, Kool M, Hassing I, Bol M, Lambrecht BN, Pieters R: Lung dendritic cells are stimulated by ultrafine particles and play a key role in particle adjuvant activity. J Allergy Clin Immunol 2008;121:1246–1254.
  31. de Heer HJ, Hammad H, Soullié T, Hijdra D, Vos N, Willart MA, Hoogsteden HC, Lambrecht BN: Essential role of lung plasmacytoid dendritic cells in preventing asthmatic reactions to harmless inhaled antigen. J Exp Med 2004;200:89–98.
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  33. van Rijt LS, Jung S, Kleinjan A, Vos N, Willart M, Duez C, Hoogsteden HC, Lambrecht BN: In vivo depletion of lung CD11c (+) dendritic cells during allergen challenge abrogates the characteristic features of asthma. J Exp Med 2005;201:981–991.
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