Skip to main content
PMC home page
Occupational and Environmental Medicine logoLink to Occupational and Environmental Medicine
. 2004 May;61(5):442–447. doi: 10.1136/oem.2003.008227

Increased inflammation and altered macrophage chemotactic responses caused by two ultrafine particle types

L Renwick 1, D Brown 1, A Clouter 1, K Donaldson 1
PMCID: PMC1740792  PMID: 15090666

Abstract

Background: Ultrafine particles have been hypothesised to be an important contributing factor in the toxicity and adverse health effects of particulate air pollution (PM10) and nanoparticles are used increasingly in industrial processes.

Aims: To compare the ability of ultrafine and fine particles of titanium dioxide and carbon black to induce inflammation, cause epithelial injury, and affect the alveolar macrophage clearance functions of phagocytosis and chemotaxis in vivo.

Methods: Rats were instilled with fine and ultrafine carbon black and titanium dioxide. Inflammation was quantified by bronchoalveolar lavage; the ability of the macrophages to phagoytose indictor fluorescent beads and to migrate towards aC5a were determined.

Results: Ultrafine particles induced more PMN recruitment, epithelial damage, and cytotoxicity than their fine counterparts, exposed at equal mass. Both ultrafine and fine particles significantly impaired the phagocytic ability of alveolar macrophages. Only ultrafine particle treatment significantly enhanced the sensitivity of alveolar macrophages to chemotact towards C5a.

Conclusions: Ultrafine particles of two very different materials induced inflammation and epithelial damage to a greater extent than their fine counterparts. In general, the effect of ultrafine carbon black was greater than ultrafine titanium dioxide, suggesting that there are differences in the likely harmfulness of different types of ultrafine particle. Epithelial injury and toxicity were associated with the development of inflammation after exposure to ultrafines. Increased sensitivity to a C5a chemotactic gradient could make the ultrafine exposed macrophages more likely to be retained in the lungs, so allowing dose to accumulate.

Full Text

The Full Text of this article is available as a PDF (334.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Afaq F., Abidi P., Matin R., Rahman Q. Cytotoxicity, pro-oxidant effects and antioxidant depletion in rat lung alveolar macrophages exposed to ultrafine titanium dioxide. J Appl Toxicol. 1998 Sep-Oct;18(5):307–312. doi: 10.1002/(sici)1099-1263(1998090)18:5<307::aid-jat508>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  2. Avakian Maureen D., Dellinger Barry, Fiedler Heidelore, Gullet Brian, Koshland Catherine, Marklund Stellan, Oberdörster Günter, Safe Stephen, Sarofim Adel, Smith Kirk R. The origin, fate, and health effects of combustion by-products: a research framework. Environ Health Perspect. 2002 Nov;110(11):1155–1162. doi: 10.1289/ehp.021101155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Becker S., Soukup J. M., Gilmour M. I., Devlin R. B. Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production. Toxicol Appl Pharmacol. 1996 Dec;141(2):637–648. doi: 10.1006/taap.1996.0330. [DOI] [PubMed] [Google Scholar]
  4. Brown D. M., Stone V., Findlay P., MacNee W., Donaldson K. Increased inflammation and intracellular calcium caused by ultrafine carbon black is independent of transition metals or other soluble components. Occup Environ Med. 2000 Oct;57(10):685–691. doi: 10.1136/oem.57.10.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown D. M., Wilson M. R., MacNee W., Stone V., Donaldson K. Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol Appl Pharmacol. 2001 Sep 15;175(3):191–199. doi: 10.1006/taap.2001.9240. [DOI] [PubMed] [Google Scholar]
  6. Brunekreef Bert, Holgate Stephen T. Air pollution and health. Lancet. 2002 Oct 19;360(9341):1233–1242. doi: 10.1016/S0140-6736(02)11274-8. [DOI] [PubMed] [Google Scholar]
  7. Clouter A., Houghton C. E., Bowskill C. A., Hoskins J. A., Brown R. C. An in vitro/in vivo study into the short term effects of exposure to mineral fibres. Exp Toxicol Pathol. 1996 Nov;48(6):484–486. doi: 10.1016/S0940-2993(96)80061-3. [DOI] [PubMed] [Google Scholar]
  8. Costa D. L., Dreher K. L. Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. Environ Health Perspect. 1997 Sep;105 (Suppl 5):1053–1060. doi: 10.1289/ehp.97105s51053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dick Colin A. J., Brown David M., Donaldson Ken, Stone Vicki. The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types. Inhal Toxicol. 2003 Jan;15(1):39–52. doi: 10.1080/08958370304454. [DOI] [PubMed] [Google Scholar]
  10. Dick Colin A. J., Brown David M., Donaldson Ken, Stone Vicki. The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types. Inhal Toxicol. 2003 Jan;15(1):39–52. doi: 10.1080/08958370304454. [DOI] [PubMed] [Google Scholar]
  11. Donaldson K., Brown G. M., Brown D. M., Slight J., Robertson M. D., Davis J. M. Impaired chemotactic responses of bronchoalveolar leukocytes in experimental pneumoconiosis. J Pathol. 1990 Jan;160(1):63–69. doi: 10.1002/path.1711600113. [DOI] [PubMed] [Google Scholar]
  12. Donaldson K., Stone V., Clouter A., Renwick L., MacNee W. Ultrafine particles. Occup Environ Med. 2001 Mar;58(3):211-6, 199. doi: 10.1136/oem.58.3.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Donaldson Ken, Brown David, Clouter Anna, Duffin Rodger, MacNee William, Renwick Louise, Tran Lang, Stone Vicki. The pulmonary toxicology of ultrafine particles. J Aerosol Med. 2002 Summer;15(2):213–220. doi: 10.1089/089426802320282338. [DOI] [PubMed] [Google Scholar]
  14. Donaldson Ken, Tran C. Lang. Inflammation caused by particles and fibers. Inhal Toxicol. 2002 Jan;14(1):5–27. doi: 10.1080/089583701753338613. [DOI] [PubMed] [Google Scholar]
  15. Ferin J., Oberdörster G., Penney D. P. Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol. 1992 May;6(5):535–542. doi: 10.1165/ajrcmb/6.5.535. [DOI] [PubMed] [Google Scholar]
  16. Ferin J., Oberdörster G., Penney D. P. Pulmonary retention of ultrafine and fine particles in rats. Am J Respir Cell Mol Biol. 1992 May;6(5):535–542. doi: 10.1165/ajrcmb/6.5.535. [DOI] [PubMed] [Google Scholar]
  17. Fubini B., Mollo L., Giamello E. Free radical generation at the solid/liquid interface in iron containing minerals. Free Radic Res. 1995 Dec;23(6):593–614. doi: 10.3109/10715769509065280. [DOI] [PubMed] [Google Scholar]
  18. Gilmour P. S., Brown D. M., Lindsay T. G., Beswick P. H., MacNee W., Donaldson K. Adverse health effects of PM10 particles: involvement of iron in generation of hydroxyl radical. Occup Environ Med. 1996 Dec;53(12):817–822. doi: 10.1136/oem.53.12.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Governa M., Amati M., Valentino M., Visonà I., Fubini B., Botta G. C., Volpe A. R., Carmignani M. In vitro cleavage by asbestos fibers of the fifth component of human complement through free-radical generation and kallikrein activation. J Toxicol Environ Health A. 2000 Apr 14;59(7):539–552. doi: 10.1080/009841000156664. [DOI] [PubMed] [Google Scholar]
  20. Harper R. A., Stirling C., Townsend K. M., Kreyling W. G., Patrick G. Intracellular particle dissolution in macrophages isolated from the lung of the Fischer (F-344) rat. Exp Lung Res. 1994 Mar-Apr;20(2):143–156. doi: 10.3109/01902149409064379. [DOI] [PubMed] [Google Scholar]
  21. Hatherill J. R., Stephens K. E., Nagao K., Ishizaka A., Wilmarth L., Wang J. C., Deinhart T., Larrick J. W., Raffin T. A. Effects of anti-C5a antibodies on human polymorphonuclear leukocyte function: chemotaxis, chemiluminescence, and lysosomal enzyme release. J Biol Response Mod. 1989 Dec;8(6):614–624. [PubMed] [Google Scholar]
  22. Jiménez L. A., Thompson J., Brown D. A., Rahman I., Antonicelli F., Duffin R., Drost E. M., Hay R. T., Donaldson K., MacNee W. Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation. Toxicol Appl Pharmacol. 2000 Jul 15;166(2):101–110. doi: 10.1006/taap.2000.8957. [DOI] [PubMed] [Google Scholar]
  23. Lighty J. S., Veranth J. M., Sarofim A. F. Combustion aerosols: factors governing their size and composition and implications to human health. J Air Waste Manag Assoc. 2000 Sep;50(9):1565–1622. doi: 10.1080/10473289.2000.10464197. [DOI] [PubMed] [Google Scholar]
  24. Renwick L. C., Donaldson K., Clouter A. Impairment of alveolar macrophage phagocytosis by ultrafine particles. Toxicol Appl Pharmacol. 2001 Apr 15;172(2):119–127. doi: 10.1006/taap.2001.9128. [DOI] [PubMed] [Google Scholar]
  25. Renwick L. C., Donaldson K., Clouter A. Impairment of alveolar macrophage phagocytosis by ultrafine particles. Toxicol Appl Pharmacol. 2001 Apr 15;172(2):119–127. doi: 10.1006/taap.2001.9128. [DOI] [PubMed] [Google Scholar]
  26. Strunk R. C., Eidlen D. M., Mason R. J. Pulmonary alveolar type II epithelial cells synthesize and secrete proteins of the classical and alternative complement pathways. J Clin Invest. 1988 May;81(5):1419–1426. doi: 10.1172/JCI113472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Wilson Martin R., Lightbody Janet H., Donaldson Ken, Sales Jill, Stone Vicki. Interactions between ultrafine particles and transition metals in vivo and in vitro. Toxicol Appl Pharmacol. 2002 Nov 1;184(3):172–179. doi: 10.1006/taap.2002.9501. [DOI] [PubMed] [Google Scholar]
  28. Zhang Q., Kusaka Y., Sato K., Nakakuki K., Kohyama N., Donaldson K. Differences in the extent of inflammation caused by intratracheal exposure to three ultrafine metals: role of free radicals. J Toxicol Environ Health A. 1998 Mar 27;53(6):423–438. doi: 10.1080/009841098159169. [DOI] [PubMed] [Google Scholar]

Articles from Occupational and Environmental Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES