, Volume 27, Issue 2, pp 97–105

Endotoxin as modifier of particulate matter toxicity: a review of the literature

  • Cristiane Degobbi
  • Paulo Hilário Nascimento Saldiva
  • Christine Rogers
Review Paper


It is well known that particulate matter (PM) and endotoxin are able to trigger inflammatory responses in the lung. Most studies have focused on the components separately and on the identification of chemical components associated with PM. However, since biological components may represent around 20% of airborne PM, and endotoxin may reach concentrations as high as 30 EU/mg, recent studies have focused attention on the characterization of endotoxin present in PM and health effects. Most of the literature has suggested that endotoxin adsorbed in PM is able to elicit immunological responses associated with increase in pro-inflammatory cytokine expression. The aim of this paper is to provide an up to date review of the findings involving toxicity effects of endotoxin associated with PM.


Endotoxin Particulate matter Cytokines Health effects 


  1. Alexis, N. E., Lay, J. C., Almond, M., & Peden, D. B. (2004). Inhalation of low-dose endotoxin favors local T(H)2 response and primes airway phagocytes in vivo. Journal of Allergy and Clinical Immunology, 114(6), 1325–1331.CrossRefGoogle Scholar
  2. Alexis, N. E., Lay, J. C., Zeman, K., Bennett, W. E., Peden, D. B., Soukup, J. M., et al. (2006). Biological material on inhaled coarse fraction particulate matter activates airway phagocytes in vivo in healthy volunteers. Journal of Allergy and Clinical Immunology, 117(6), 1396–1403.CrossRefGoogle Scholar
  3. Alfaro-Moreno, E., Martinez, L., Garcia-Cuellar, C., Bonner, J. C., Murray, J. C., Rosas, I., et al. (2002). Biologic effects induced in vitro by PM10 from three different zones of Mexico City. Environmental Health Perspectives, 110(7), 715–720.CrossRefGoogle Scholar
  4. Alfaro-Moreno, E., Nawrot, T. S., Nemmar, A., & Nemery, B. (2007). Particulate matter in the environment: Pulmonary and cardiovascular effects. Current Opinion ín Pulmonary Medicine, 13(2), 98–106.CrossRefGoogle Scholar
  5. Aw, J., & Kleeman, M. J. (2003). Evaluating the first-order effect of intraannual temperature variability on urban air pollution. Journal of Geophysical Research, 108(D12), 4365.CrossRefGoogle Scholar
  6. Becker, S., Soukup, J. M., Gilmour, M. I., & Devlin, R. B. (1996). Stimulation of human and rat alveolar macrophages by urban air particulates: Effects on oxidant radical generation and cytokine production. Toxicology and Applied Pharmacology, 141(2), 637–648.CrossRefGoogle Scholar
  7. Becker, S., Fenton, M. J., & Soukup, J. M. (2002). Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles. American Journal of Respiratory Cell and Molecular Biology, 27(5), 611–618.Google Scholar
  8. Becker, S., Soukup, J. M., Sioutas, C., & Cassee, F. R. (2003). Response of human alveolar macrophages to ultrafine, fine, and coarse urban air pollution particles. Experimental Lung Research, 29(1), 29–44.CrossRefGoogle Scholar
  9. Bolte, G., Bischof, W., Borte, M., Lehmann, I., Wichmann, H. E., & Heinrich, J. (2003). Early endotoxin exposure and atopy development in infants: Results of a birth cohort study. Journal of Clinical & Experimental Allergy, 33(6), 770–776.CrossRefGoogle Scholar
  10. Bonner, J. C., Rice, A. B., Lindroos, P. M., O’Brien, P. O., Dreher, K. L., Rosas, I., et al. (1998). Induction of the lung myofibroblast PDGF receptor system by urban ambient particles from Mexico City. American Journal of Respiratory Cell and Molecular Biology, 19(4), 672–680.Google Scholar
  11. Braga, C. R., Rizzo, M. C., Naspitz, C. K., & Sole, D. (2004). Nasal provocation test (NPT) with isolated and associated dermatophagoides pteronyssinus (Dp) and endotoxin lipopolysaccharide (LPS) in children with allergic rhinitis (AR) and nonallergic controls. Journal of Investigational Allergology and Clinical Immunology, 14(2), 142–148.Google Scholar
  12. Braun-Fahrlander, C., Riedler, J., Herz, U., Eder, W., Waser, M., Grize, L., et al. (2002). Environmental exposure to endotoxin and its relation to asthma in school-age children. New England Journal of Medicine, 347(12), 869–877.CrossRefGoogle Scholar
  13. Carlton, A. G., Pinder, R. W., Bhave, P. V., & Pouliot, G. A. (2010). To What Extent Can Biogenic SOA be Controlled? Environmental Science Technology, Epub ahead of print.Google Scholar
  14. Carty, C. L., Gehring, U., Cyrys, J., Bischof, W., & Heinrich, J. (2003). Seasonal variability of endotoxin in ambient fine particulate matter. Journal of Environmental Monitoring, 5(6), 953–958.CrossRefGoogle Scholar
  15. Carvalho-Oliveira, R., Pozo, R. M., Lobo, D. J., Lichtenfels, A. J., Martins-Junior, H. A., Bustilho, J. O., et al. (2005). Diesel emissions significantly influence composition and mutagenicity of ambient particles: A case study in Sao Paulo, Brazil. Environmental Research, 98(1), 1–7.CrossRefGoogle Scholar
  16. Chow, J. C., Watson, J. G., Edgerton, S. A., & Vega, E. (2002). Chemical composition of PM2.5 and PM10 in Mexico City during winter 1997. Science of the Total Environment, 287(3), 177–201.CrossRefGoogle Scholar
  17. Dales, R., Miller, D., Ruest, K., Guay, M., & Judek, S. (2006). Airborne endotoxin is associated with respiratory illness in the first 2 years of life. Environmental Health Perspectives, 114(4), 610–614.CrossRefGoogle Scholar
  18. Daniels, A. U., Barnes, F. H., Charlebois, S. J., & Smith, R. A. (2000). Macrophage cytokine response to particles and lipopolysaccharide in vitro. Journal of Biomedical Materials Research, 49(4), 469–478.CrossRefGoogle Scholar
  19. Dong, W., Lewtas, J., & Luster, M. I. (1996). Role of endotoxin in tumor necrosis factor alpha expression from alveolar macrophages treated with urban air particles. Experimental Lung Research, 22(5), 577–592.CrossRefGoogle Scholar
  20. Douwes, J., Pearce, N., & Heederik, D. (2002). Does environmental endotoxin exposure prevent asthma? Thorax, 57(1), 86–90.CrossRefGoogle Scholar
  21. Edgerton, E. S., Hartsell, B. E., Saylor, R. D., Jansen, J. J., Hansen, D. A., & Hidy, G. M. (2006). The southeastern aerosol research and characterization study, part 3: Continuous measurements of fine particulate matter mass and composition. Journal of the Air & Waste Management Association, 56(9), 1325–1341.Google Scholar
  22. Eisenbarth, S. C., Piggott, D. A., Huleatt, J. W., Visintin, I., Herrick, C. A., & Bottomly, K. (2002). Lipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen. Journal of Experimental Medicine, 196(12), 1645–1651.CrossRefGoogle Scholar
  23. Eldridge, M. W., & Peden, D. B. (2000). Airway response to concomitant exposure with endotoxin and allergen in atopic asthmatics. Journal of Toxicology and Environmental Health, part A, 61(1), 27–37.CrossRefGoogle Scholar
  24. Franklin, M., Koutrakis, P., & Schwartz, P. (2008). The role of particle composition on the association between PM2.5 and mortality. Epidemiology, 19(5), 680–689.CrossRefGoogle Scholar
  25. Gereda, J. E., Leung, D. Y., Thatayatikom, A., Streib, J. E., Price, M. R., Klinnert, M. D., et al. (2000). Relation between house-dust endotoxin exposure, type 1 T-cell development, and allergen sensitisation in infants at high risk of asthma. Lancet, 355(9216), 1680–1683.CrossRefGoogle Scholar
  26. Gillespie, J., Wickens, K., Siebers, R., Howden-Chapman, P., Town, I., Epton, M., et al. (2006). Endotoxin exposure, wheezing, and rash in infancy in a New Zealand birth cohort. Journal of Allergy and Clinical Immunology, 118(6), 1265–1270.CrossRefGoogle Scholar
  27. Harkema, J. R., & Wagner, J. G. (2005). Epithelial and inflammatory responses in the airways of laboratory rats coexposed to ozone and biogenic substances: Enhancement of toxicant-induced airway injury. Experimental and Toxicologic Pathology, 57(Suppl 1), 129–141.CrossRefGoogle Scholar
  28. Heinrich, J., Pitz, M., Bischof, W., Krug, N., & Borm, P. J. A. (2003). Endotoxin in fine (PM sub(2.5)) and coarse (PM sub(2.5–10)) particle mass of ambient aerosols. A temporo-spatial analysis. Atmospheric Environment, 37(26), 3659–3667.CrossRefGoogle Scholar
  29. Hetland, R. B., Cassee, F. R., Lag, M., Refsnes, M., Dybing, E., & Schwarze, P. E. (2005). Cytokine release from alveolar macrophages exposed to ambient particulate matter: Heterogeneity in relation to size, city and season. Particle and Fibre Toxicology, 2, 4.CrossRefGoogle Scholar
  30. Huang, S. L., Cheng, W. L., Lee, C. T., Huang, H. C., & Chan, C. C. (2002). Contribution of endotoxin in macrophage cytokine response to ambient particles in vitro. Journal of Toxicology and Environmental Health, part A, 65(17), 1261–1272.CrossRefGoogle Scholar
  31. Imrich, A., Ning, Y. Y., Koziel, H., Coull, B., & Kobzik, L. (1999). Lipopolysaccharide priming amplifies lung macrophage tumor necrosis factor production in response to air particles. Toxicology and Applied Pharmacology, 159(2), 117–124.CrossRefGoogle Scholar
  32. Imrich, A., Ning, Y., & Kobzik, L. (2000). Insoluble components of concentrated air particles mediate alveolar macrophage responses in vitro. Toxicology and Applied Pharmacology, 167(2), 140–150.CrossRefGoogle Scholar
  33. Kabir, K., Gelinas, J. P., Chen, M., Chen, D., Zhang, D., Luo, X., et al. (2002). Characterization of a murine model of endotoxin-induced acute lung injury. Shock, 17(4), 300–303.CrossRefGoogle Scholar
  34. Katsouyanni, K., Touloumi, G., Samoli, E., Gryparis, A., Le Tertre, A., Monopolis, Y., et al. (2001). Confounding and effect modification in the short-term effects of ambient particles on total mortality: Results from 29 European cities within the APHEA2 project. Epidemiology, 12(5), 521–531.CrossRefGoogle Scholar
  35. Kim, B. M., Teffera, S., & Zeldin, M. D. (2000). Characterization of PM2.5 and PM10 in the South Coast Air Basin of southern California: Part 1–spatial variations. Journal of the Air & Waste Management Association, 50(12), 2034–2044.Google Scholar
  36. Kitchens, R. L. (2000). Role of CD14 in cellular recognition of bacterial lipopolysaccharides. Chemical Immunology, 74, 61–82.CrossRefGoogle Scholar
  37. Kline, J. N., Cowden, J. D., Hunninghake, G. W., Schutte, B. C., Watt, J. L., Wohlford-Lenane, C. L., et al. (1999). Variable airway responsiveness to inhaled lipopolysaccharide. American Journal of Respiratory and Critical Care Medicine, 160(1), 297–303.Google Scholar
  38. Latha, K. M., & Badarinath, K. V. (2005). Seasonal variations of PM10 and PM2.5 particles loading over tropical urban environment. International Journal of Environmental Health Research, 15(1), 63–68.CrossRefGoogle Scholar
  39. Liu, A. H. (2002). Endotoxin exposure in allergy and asthma: Reconciling a paradox. Journal of Allergy and Clinical Immunology, 109(3), 379–392.CrossRefGoogle Scholar
  40. Liu, A. H., & Redmon, A. H., Jr. (2001). Endotoxin: friend or foe? Allergy and Asthma Proceedings, 22(6), 337–340.Google Scholar
  41. Long, C. M., Suh, H. H., Kobzik, L., Catalano, P. J., Ning, Y. Y., & Koutrakis, P. (2001). A pilot investigation of the relative toxicity of indoor and outdoor fine particles: In vitro effects of endotoxin and other particulate properties. Environmental Health Perspectives, 109(10), 1019–1026.CrossRefGoogle Scholar
  42. Matthias-Maser, S., Obolkin, V., Khodzer, T., & Jaenicke, R. (2000). Seasonal variation of primary biological aerosol particles in the remote continental region of Lake Baikal/Siberia. Atmospheric Environment, 34(22), 3805–3811.CrossRefGoogle Scholar
  43. Michel, O., Ginanni, R., Duchateau, J., Vertongen, F., Le Bon, B., & Sergysels, R. (1991). Domestic endotoxin exposure and clinical severity of asthma. Clinical & Experimental Allergy, 21(4), 441–448.CrossRefGoogle Scholar
  44. Miller, S. I., Ernst, R. K., & Bader, M. W. (2005). LPS, TLR4 and infectious disease diversity. Nature Reviews. Microbiology, 3(1), 36–46.CrossRefGoogle Scholar
  45. Monn, C., & Becker, S. (1999). Cytotoxicity and induction of proinflammatory cytokines from human monocytes exposed to fine (PM2.5) and coarse particles (PM10–2.5) in outdoor and indoor air. Toxicology and Applied Pharmacology, 155(3), 245–252.CrossRefGoogle Scholar
  46. Monn, C., & Koren, H. S. (1999). Bioaerosols in ambient air particulates: a review and research needs. Reviews on Environmental Health, 14(2), 79–89.Google Scholar
  47. Mudway, I. S., Guastadisegni, C., Kelly, F. J., Cassee, F. R., Gerlofs-Nijland, M. E., Janssen, N. A. H. et al. (2010). Determinants of The Pro-Inflammatory Action of Ambient Particulate Matter in Immortalised Murine Macrophages. Environmental Health Perspectives. doi:10.1289/ehp.1002105.
  48. Mueller-Anneling, L., Avol, E., Peters, J. M., & Thorne, P. S. (2004). Ambient endotoxin concentrations in PM10 from Southern California. Environmental Health Perspectives, 112(5), 583–588.CrossRefGoogle Scholar
  49. Murray, P. R., Baron, E. J., Jorgensen, J. H., Landry, M. L., & Pfaller, M. A. (2007). Manual fo Clinical Microbiology. Washington: American Society Microbiology.Google Scholar
  50. Ning, Y., Imrich, A., Goldsmith, C. A., Qin, G., & Kobzik, L. (2000). Alveolar macrophage cytokine production in response to air particles in vitro: role of endotoxin. Journal of Toxicology and Environmental Health, part A, 59(3), 165–180.CrossRefGoogle Scholar
  51. Osornio-Vargas, A. R., Bonner, J. C., Alfaro-Moreno, E., Martinez, L., Garcia-Cuellar, C., Ponce-de-Leon Rosales, S., et al. (2003). Proinflammatory and cytotoxic effects of Mexico City air pollution particulate matter in vitro are dependent on particle size and composition. Environmental Health Perspectives, 111(10), 1289–1293.CrossRefGoogle Scholar
  52. Ostro, B., Feng, W. Y., Broadwin, R., Green, S., & Lipsett, M. (2007). The effects of components of fine particulate air pollution on mortality in california: Results from CALFINE. Environmental Health Perspectives, 115(1), 13–19.CrossRefGoogle Scholar
  53. Park, J. H., Gold, D. R., Spiegelman, D. L., Burge, H. A., & Milton, D. K. (2001). House dust endotoxin and wheeze in the first year of life. American Journal of Respiratory and Critical Care Medicine, 163(2), 322–328.Google Scholar
  54. Park, J. H., Cox-Ganser, J., Rao, C., & Kreiss, K. (2006). Fungal and endotoxin measurements in dust associated with respiratory symptoms in a water-damaged office building. Indoor Air, 16(3), 192–203.CrossRefGoogle Scholar
  55. Park, K., Kim, J. S., & Park, S. H. (2009). Measurements of hygroscopicity and volatility of atmospheric ultrafine particles during ultrafine particle formation events at urban, industrial, and coastal sites. Environmental Science Technology, 43(17), 6710–6716.CrossRefGoogle Scholar
  56. Perzanowski, M. S., Miller, R. L., Thorne, P. S., Barr, R. G., Divjan, A., Sheares, B. J., et al. (2006). Endotoxin in inner-city homes: Associations with wheeze and eczema in early childhood. Journal of Allergy and Clinical Immunology, 117(5), 1082–1089.CrossRefGoogle Scholar
  57. Pope, C. A., 3rd, Burnett, R. T., Thurston, G. D., Thun, M. J., Calle, E. E., Krewski, D., et al. (2004). Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation, 109(1), 71–77.CrossRefGoogle Scholar
  58. Pope, C. A., 3rd, Ezzati, M., & Dockery, D. W. (2009). Fine-particulate air pollution and life expectancy in the United States. New England Journal of Medicine, 360(4), 376–386.CrossRefGoogle Scholar
  59. Preas, H. L., 2nd, Jubran, A., Vandivier, R. W., Reda, D., Godin, P. J., Banks, S. M., et al. (2001). Effect of endotoxin on ventilation and breath variability: Role of cyclooxygenase pathway. American Journal of Respiratory and Critical Care Medicine, 164(4), 620–626.Google Scholar
  60. Rizzo, M. C., Naspitz, C. K., Fernandez-Caldas, E., Lockey, R. F., Mimica, I., & Sole, D. (1997). Endotoxin exposure and symptoms in asthmatic children. Pediatric Allergy & Immunology, 8(3), 121–126.CrossRefGoogle Scholar
  61. Rylander, R., & Holt, P. G. (1998). (1– > 3)-beta-D-glucan and endotoxin modulate immune response to inhaled allergen. Mediators of Inflammation, 7(2), 105–110.CrossRefGoogle Scholar
  62. Saldiva, P. H., Clarke, R. W., Coull, B. A., Stearns, R. C., Lawrence, J., Murthy, G. G., et al. (2002). Lung inflammation induced by concentrated ambient air particles is related to particle composition. American Journal of Respiratory and Critical Care Medicine, 165(12), 1610–1617.CrossRefGoogle Scholar
  63. Samet, J. M., Zeger, S. L., Dominici, F., Curriero, F., Coursac, I., Dockery, D. W. et al. (2000). The National Morbidity, Mortality, and Air Pollution Study. Part II: Morbidity and mortality from air pollution in the United States. Research Report Health Effects Institute, 94(Pt 2), 5-70; discussion 71–79.Google Scholar
  64. Schins, R. P., Lightbody, J. H., Borm, P. J., Shi, T., Donaldson, K., & Stone, V. (2004). Inflammatory effects of coarse and fine particulate matter in relation to chemical and biological constituents. Toxicology and Applied Pharmacology, 195(1), 1–11.CrossRefGoogle Scholar
  65. Smid, T., Heederik, D., Houba, R., & Quanjer, P. H. (1994). Dust- and endotoxin-related acute lung function changes and work-related symptoms in workers in the animal feed industry. American Journal of Industrial Medicine, 25(6), 877–888.CrossRefGoogle Scholar
  66. Soukup, J. M., & Becker, S. (2001). Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin. Toxicology and Applied Pharmacology, 171(1), 20–26.CrossRefGoogle Scholar
  67. Steerenberg, P. A., Withagen, C. E., van Dalen, W. J., Dormans, J. A., Cassee, F. R., Heisterkamp, S. H., et al. (2004). Adjuvant activity of ambient particulate matter of different sites, sizes, and seasons in a respiratory allergy mouse model. Toxicology and Applied Pharmacology, 200(3), 186–200.CrossRefGoogle Scholar
  68. Trent, M. S., Stead, C. M., Tran, A. X., & Hankins, J. V. (2006). Diversity of endotoxin and its impact on pathogenesis. Journal of Endotoxin Research, 12(4), 205–223.CrossRefGoogle Scholar
  69. Turnbull, A. B., & Harrison, R. M. (2000). Major component contributions to PM10 composition in the UK atmosphere. Atmospheric Environment, 34(19), 3129–3137.CrossRefGoogle Scholar
  70. Vallius, M., Janssen, N. A., Heinrich, J., Hoek, G., Ruuskanen, J., Cyrys, J., et al. (2005). Sources and elemental composition of ambient PM(2.5) in three European cities. Science of the Total Environment, 337(1–3), 147–162.CrossRefGoogle Scholar
  71. von Mutius, E., Braun-Fahrlander, C., Schierl, R., Riedler, J., Ehlermann, S., Maisch, S., et al. (2000). Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clinical & Experimental Allergy, 30(9), 1230–1234.CrossRefGoogle Scholar
  72. Wagner, J. G., Hotchkiss, J. A., & Harkema, J. R. (2001). Effects of ozone and endotoxin coexposure on rat airway epithelium: Potentiation of toxicant-induced alterations. Environmental Health Perspectives, 109(Suppl 4), 591–598.CrossRefGoogle Scholar
  73. Wan, G. H., & Li, C. S. (1999). Indoor endotoxin and glucan in association with airway inflammation and systemic symptoms. Archives of Environmental Health, 54(3), 172–179.CrossRefGoogle Scholar
  74. Wang, X., Bi, X., Sheng, G., & Fu, J. (2006). Chemical composition and sources of PM10 and PM2.5 aerosols in Guangzhou, China. Environmental Monitoring and Assessment, 119(1–3), 425–439.CrossRefGoogle Scholar
  75. WHO. (2005). Air quality guidelines. Global update (p. 496). NY: World Health Organization.Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Cristiane Degobbi
    • 1
  • Paulo Hilário Nascimento Saldiva
    • 1
  • Christine Rogers
    • 2
  1. 1.Laboratory of Experimental Air Pollution, Department of Pathology, Medical SchoolUniversity of Sao PauloSao PauloBrazil
  2. 2.Environmental Health Sciences, School of Public Health and Health SciencesUniversity of MassachusettsAmherstUSA

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