Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Reactive oxygen species- and nitric oxide-mediated lung inflammation and mitochondrial dysfunction in wild-type and iNOS-deficient mice exposed to diesel exhaust particles.

Authors
Zhao-H; Ma-JK; Barger-MW; Mercer-RR; Millecchia-L; Schwegler-Berry-D; Castranova-V; Ma-JY
Source
J Toxicol Environ Health, A 2009 Jan; 72(8):560-570
NIOSHTIC No.
20035121
Abstract
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.
Keywords
Biological-effects; Biological-factors; Biological-monitoring; Cell-biology; Cell-damage; Cell-function; Cellular-reactions; Cell-morphology; Diesel-emissions; Inhalation-studies; Laboratory-animals; Lung-cells; Lung-disorders; Lung-irritants; Laboratory-testing; Musculoskeletal-system; Musculoskeletal-system-disorders; Particle-aerodynamics; Physical-reactions; Pulmonary-disorders; Pulmonary-system-disorders; Risk-analysis; Safety-equipment
Contact
Jane Y. Ma , Health Effects Laboratory Division, PRAB, NIOSH, 1095 Willowdale Road, Morgantown, WV 26505-2888
CODEN
JTEHD6
CAS No.
10102-43-9
Publication Date
20090101
Document Type
Journal Article
Email Address
jym1@cdc.gov
Fiscal Year
2009
NTIS Accession No.
NTIS Price
Issue of Publication
8
ISSN
1528-7394
NIOSH Division
HELD
Priority Area
Transportation, Warehousing and Utilities
Source Name
Journal of Toxicology and Environmental Health, Part A: Current Issues
State
WV
TOP