Particle-Induced Lung Inflammation and Extracellular EC-SODEPA Grant Number: R825702C006
Subproject: this is subproject number 006 , established and managed by the Center Director under grant R825702
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Environmental Lung Disease Center (National Jewish Medical and Research Center)
Center Director: Mason, Robert J.
Title: Particle-Induced Lung Inflammation and Extracellular EC-SOD
Investigators: Crapo, James D. , Chang, Ling-Yi
Institution: National Jewish Medical and Research Center
EPA Project Officer: Chung, Serena
Project Period: February 16, 1998 through February 28, 2003 (Extended to February 28, 2004)
RFA: Environmental Lung Disease Center (National Jewish Medical and Research Center) (1998) RFA Text | Recipients Lists
Research Category: Targeted Research
Airborne particles in industrialized and urban areas range from innocuous dusts to condensations of a variety of chemical toxicants. Particle concentration may be an order of magnitude higher in cities and urban areas than remote areas. Epidemiology studies have demonstrated a significant association between these high particle levels and adverse human health effects. As yet no mechanism has been found to explain these effects. Antioxidant defense mechanisms have been implicated as important factors in protection from lung injury by particulate-generated oxidants and in protection from oxidants generated during particle phagocytosis and clearance. A deficiency in the lung's ability to scavenge oxygen-derived metabolites may enhance the adverse reactions to inhaled particles. Of the antioxidant defenses in the lung, extracellular superoxide dismutase (EC- SOD) is of particular interest because it is present in the lung in a high concentration and at a location uniquely efficient for scavenging inflammatory cell-released superoxide. We hypothesize that inflammatory responses in the lung following particle exposure are critically dependent on EC-SOD. The extent of inflammatory mediator release following particle exposure and the resultant lung injury or dysfunction is hypothesized to be reversely related to EC-SOD concentration in the lung. We further hypothesize that EC-SOD modulation of nitric oxide availability is an important mechanism of its protective functions. To test our hypotheses, we will use transgenic mice that over- and under-express lung EC-SOD. Lung epithelial and/or interstitial thickening induced by particle exposure, in particular in EC-SOD deficient individuals will be evaluated using morphometric analyses. These studies will reveal potential pathways for the control of particle-induced lung injury with topically applied extracellular antioxidants.
Supplemental Keywords:RFA, Health, Scientific Discipline, Air, particulate matter, Toxicology, Environmental Chemistry, Risk Assessments, Disease & Cumulative Effects, Biochemistry, ambient air quality, health effects, particulates, urban air, antioxidants, morphometric analyses, air pollutants, human health effects, lung, lung disease, airway disease, ambient air, air pollution, oxidants, human exposure, lung dysfunction, lung inflammation, particulate exposure, environmental stressors, harmful environmental agents, ambient particulates, extracellular SOD, human health risk
Progress and Final Reports:
Main Center Abstract and Reports:R825702 Environmental Lung Disease Center (National Jewish Medical and Research Center)
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R825702C001 SP-A and SP-D in Environmental Lung Disease
R825702C003 Adaptation to Nitrogen Dioxide: Role of Altered Glycolytic Pathway Enzyme Expression and NF-κB-Dependent Cellular Defenses Against Apoptosis
R825702C005 Inhalation of Particulate Matter Alters the Allergic Airway Response to Inhaled Allergen
R825702C006 Particle-Induced Lung Inflammation and Extracellular EC-SOD
R825702C007 Indoor-Outdoor Relationships of Airborne Particle Count and Endotoxin Concentrations
R825702C008 The Role of Mitochondrial DNA Mutations in Oxidant-Mediated Lung Injury
R825702C009 Immunopathogenesis of Hypersensitivity Pneumonitis in the Mouse
R825702C010 Activation of Natural T Lymphocytes by Diesel Exhaust Particulates Leads to Their Production of Interleukin-4 and TH2 Lymphocyte Differentiation to Allergen
R825702C011 Latex Antigen Levels During Powdered and Powderless Glove Use
R825702C012 Adjuvant Effects of Ozone in a Model of Allergen-Induced Airway Inflammation and Hyperresponsiveness
R825702C013 Acute Exposure to Particulate Air Pollution in Childhood Asthma
R825702C014 Mechanisms of Ozone Toxicity to the Lung