Environmental Health Perspectives 105, Supplement 5, September 1997

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The Role of Reactive Oxygen and Nitrogen Species in the Response of Airway Epithelium to Particulates

Linda D. Martin, 1 Thomas M. Krunkosky, 1 Janice A. Dye, 2 Bernard M. Fischer, 1 Nan Fei Jiang, 1 Lori G. Rochelle, 1 Nancy J. Akley, 1 Kevin L. Dreher, 2 and Kenneth B. Adler 1

1 College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina
2 National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina

Abstract
Epidemiologic and occupational studies indicate adverse health effects due to inhalation of particulate air pollutants, but precise biologic mechanisms responsible have yet to be fully established. The tracheobronchial epithelium forms the body's first physiologic barrier to such airborne pollutants, where ciliary movement functions to remove the offending substances caught in the overlying mucus layer. Resident and infiltrating phagocytic cells also function in this removal process. In this paper, we examine the role of reactive oxygen and nitrogen species (ROS/RNS) in the response of airway epithelium to particulates. Some particulates themselves can generate ROS, as can the epithelial cells, in response to appropriate stimulation. In addition, resident macrophages in the airways and the alveolar spaces can release ROS/RNS after phagocytosis of inhaled particles. These macrophages also release large amounts of tumor necrosis factor alpha (TNF- alpha ), a cytokine that can generate responses within the airway epithelium dependent upon intracellular generation of ROS/RNS. As a result, signal transduction pathways are set in motion that may contribute to inflammation and other pathobiology in the airway. Such effects include increased expression of intercellular adhesion molecule 1, interleukin-6, cytosolic and inducible nitric oxide synthase, manganese superoxide dismutase, cytosolic phospholipase A 2 , and hypersecretion of mucus. Ultimately, ROS/RNS may play a role in the global response of the airway epithelium to particulate pollutants via activation of kinases and transcription factors common to many response genes. Thus, defense mechanisms involved in responding to offending particulates may result in a complex cascade of events that can contribute to airway pathology. -- Environ Health Perspect 105(Suppl 5):1301-1307 (1997)

Key words : reactive oxygen/nitrogen species, signal transduction, airway inflammation, mucin hypersecretion, ICAM-1, TNF- alpha

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 27 March 1997; accepted 15 June 1997.

This work was supported by National Institutes of Health grants HL 36982, HL 09063, and HL 09512; and grants from GlaxoWellcome, Inc. and the state of North Carolina.

This report has been reviewed by the National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the agency.

Address correspondence to Dr. K.B. Adler, Department of Anatomy, Physiological Sciences, and Radiology. North Carolina State University, College of Veterinary Medicine, 4700 Hillsborough Street, Raleigh, NC 27606. Telephone: (919) 821-9549. Fax: (919) 829-4465. E-mail: kadler@sn1.cvm.ncsu.edu

Abbreviations used: DMTU, dimethylthiourea; GM-CSF, granulocyte-macrophage colony stimulating factor; GPTE, guinea pig tracheal epithelial; H 2 O 2 , hydrogen peroxide; HO·, hydroxyl radical; ICAM-1, intracellular adhesion molecule 1;IL-1, interleukin 1; IL-6, interleukin 6; IL-8, interleukin 8; iNOS, inducible nitric oxide synthase; LNMA, l- N 6 -monomethylarginine; MnSOD, manganese superoxide dismutase; NF kappa B, nuclear factor kappa B; NO·, nitric oxide; O 2 · - , superoxide; ONOO - , peroxynitrite; P+XO, purine + xanthine oxidase; PC-PLC, phosphatidylcholine-specific phospholipase C; PKC, protein kinase C; PKG, cGMP-dependent protein kinase; PLA 2 , phospholipase A 2 ; RNS, reactive nitrogen species; ROFA, residual oil fly ash; ROS, reactive oxygen species; RTE, rat tracheal epithelial; SiO 2 , silica; SOD, superoxide dismutase; TNF- alpha , tumor necrosis factor alpha.

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Last Update: November 28, 1997