Reactive Oxygen Species- and Nitric Oxide-Mediated Lung Inflammation and Mitochondrial Dysfunction in Wild-Type and iNOS-Deficient Mice Exposed to Diesel Exhaust Particles

Details

• Personal Author:
  Barger MW ; Castranova, Vincent ; Ma JK ; Ma JY ; Mercer RR ; Millecchia L ; Schwegler-Berry D ; Zhao H
• Description:
  Pulmonary responses to diesel exhaust particles (DEP) exposure are mediated through enhanced production of reactive oxygen species (ROS) and nitric oxide (NO) by alveolar macrophages (AM). The current study examined the differential roles of ROS and NO in DEP-induced lung injury using C57B/6J wild-type (WT) and inducible NO synthase knockout (iNOS KO) mice. Mice exposed by pharyngeal aspiration to DEP or carbon black particles (CB) (35 mg/kg) showed an inflammatory profile that included neutrophil infiltration, increased lactate dehydrogenase (LDH) activity, and elevated albumin content in bronchoalveolar lavage fluid (BALF) at 1, 3, and 7 d postexposure. The organic extract of DEP (DEPE) did not induce an inflammatory response. Comparing WT to iNOS KO mice, the results show that NO enhanced DEP-induced neutrophils infiltration and plasma albumin content in BALF and upregulated the production of the pro-inflammatory cytokine interleukin 12 (IL-12) by AM. DEP-exposed AM from iNOS KO mice displayed diminished production of IL-12 and, in response to ex vivo lipopolysaccharide (LPS) challenge, decreased production of IL-12 but increased production of IL-10 when compared to cells from WT mice. DEP, CB, but not DEPE, induced DNA damage and mitochondria dysfunction in AM, however, that is independent of cellular production of NO. These results demonstrate that DEP-induced immune/inflammatory responses in mice are regulated by both ROS- and NO-mediated pathways. NO did not affect ROS-mediated mitochondrial dysfunction and DNA damage but upregulated IL-12 and provided a counterbalance to the ROS-mediated adaptive stress response that downregulates IL-12 and upregulates IL-10. [Description provided by NIOSH]
• Subjects:
  Biological Factors Laboratories Lung Lung Diseases Musculoskeletal Diseases Musculoskeletal System Occupational Health Particulate Matter Respiratory System Respiratory Tract Diseases Risk Assessment Safety Vehicle Emissions

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• Keywords:
  Biological-effects Biological-factors Biological-monitoring Cell-biology Cell-damage Cell-function Cell-morphology Cellular-reactions Diesel-emissions Inhalation-studies Laboratory-animals Laboratory-testing Lung-cells Lung-disorders Lung-irritants Musculoskeletal-system Musculoskeletal-system-disorders Particle-aerodynamics Physical-reactions Pulmonary-disorders Pulmonary-system-disorders Risk-analysis Safety-equipment

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• ISSN:
  1528-7394
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  72
• Issue:
  8
• NIOSHTIC Number:
  nn:20035121
• Citation:
  J Toxicol Environ Health A 2009 Jan; 72(8):560-570
• Contact Point Address:
  Jane Y. Ma , Health Effects Laboratory Division, PRAB, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505-2888
• Email:
  jym1@cdc.gov
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Transportation, Warehousing and Utilities
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Toxicology and Environmental Health, Part A: Current Issues
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1a1cf452c869ef5351f0102140f82ff7d1cb40c1c98ab25048f657cdd91ddd9a4f20e2d0ed240bc2b1bf24d35def2892b6dba7af5eec1b4556883b6e49c92ed5
• Download URL:
  https://stacks.cdc.gov/view/cdc/187079/cdc_187079_DS1.pdf
• File Type:
  [PDF - 2.48 MB ]