Grantee Research Project Results

SP-A and SP-D in Environmental Lung Disease

EPA Grant Number: R825702C001
Subproject: this is subproject number 001 , 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: Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children
Center Director: Schwartz, David A.
Title: SP-A and SP-D in Environmental Lung Disease
Investigators: Mason, Robert P. , Cook, James L. , Voelker, Dennis R.
Current Investigators: Mason, Robert P.
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

Objective:

Surfactant proteins A (SP-A) and surfactant protein D (SP-D) are calcium dependent lectins that are emerging as important host defense molecules. We believe that the lung has a special microenvironment which regulates the inflammatory response. This is necessary because the lung must handle a high burden of air born toxins and particulates, and, if an inflammatory response were initiated with each episode of exposure, the delicate gas- exchange units of the lung would be rapidly destroyed. We hypothesize that SP-A and SP-D will be especially important in host defense for organisms which are known to colonize airways but rarely lead to pneumonia since in humans these proteins are much more expressed in the gas-exchange units of the lung than in the conducting airways. In addition, ozone has been reported to alter SP-A and inhibit some of its functions. In this proposal we will focus on the host defense properties of SP-A and SP-D. In Specific Aim 1, we will focus on the binding of SP-D to Aspergillus spores. We have recently found that SP-D but not SP-A binds to Aspergillus spores. This is one of the first observations that a major difference in binding to an organism has been observed for these two proteins. This study will determine the characteristics of the binding; the ligand(s) on Aspergillus, and the consequences of the binding in terms of host defense. The second Specific Aim will focus on the alterations of SP-A and SP-D by ozone to determine the site(s) of alteration and their physiologic consequences. In the third Specific Aim we will determine the ability of SP-A and SP-D to inhibit viral infections and cytokine production by airway epithelial cells. Respiratory viral infections are clearly a major environmental problem, and SP-A and SP-D may be important elements at minimizing infection and dampening the cytokine production by epithelial cells during an active infection. This one year proposal should allow us to make major headway in our three Specific Aims.

Publications and Presentations:

Publications have been submitted on this subproject: View all 12 publications for this subproject | View all 132 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 10 journal articles for this subproject | View all 110 journal articles for this center

Supplemental Keywords:

Health, RFA, Scientific Discipline, Air, PHYSICAL ASPECTS, Health Risk Assessment, Physical Processes, Risk Assessments, particulate matter, Environmental Chemistry, tropospheric ozone, Atmospheric Sciences, Disease & Cumulative Effects, health effects, surfactant proteins, aerosols, harmful environmental agents, lung disease, pulmonary disease, Aspergillus spores, atmospheric chemistry, lung inflammation, respiratory, human exposure, environmental health effects, lung, particulate exposure, pulmonary, particulates, airway epithelial cells, exposure, PM, air pollutants, ambient air, chronic health effects, cytokine production, ozone, air pollution, human health effects, human health risk, airway disease, ambient particulates, epithelial cells, respiratory problems, air toxics

Progress and Final Reports:

Main Center Abstract and Reports:

R825702 Denver Children’s Environmental Health Center - Environmental Determinants of Airway Disease in Children

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

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.