Environmental particulate matter formed by combustion is composed of an inertcarbonaceous particulate core and layers of adsorbed pollutant molecules. After inhalation and deposition in the lung, a portion of the burden of adsorbed pollutant molecules-those molecules present at greater than one monolayer surface coverages-will be released into pulmonary surfactant. This initial release of particle-adsorbed pollutant molecules occurs rapidly and produces a general acute exposure of the lung parenchyma to the released pollutant molecules. The remaining particulate matter stays on the lung epithelium until it is phagocytized by an alveolar macrophage. Release of the residual burden of adsorbed pollutant molecules at surface coverages of less than one monolayer occurs inside the alveolar macrophage. Polynuclear aromatic hydrocarbons (PAHs) comprise the majority of the molecules present in the first monolayer since both the carbonaceous particles and the PAHs are formed concurrently by similar chemical reactions. The hypothesis of this application is that release of strongly adsorbed pollutant molecules occurs inside the macrophage as the result of chemical reactions with reactive oxyradicals. The environmental health significance of these reactions is that they may cause the activation of some of these molecules to more toxic agents.
The specific aims of this application are to: 1. Demonstrate that release of adsorbed PAH molecules, present at surface coverages less than one monolayer on carbonaceous particles, occurs as a result of chemical reactions with reactive oxyradicals inside the alveolar macrophage. 2. Determine the reaction mechanisms responsible for this intra-macrophage release.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES003156-08
Application #
2153236
Study Section
Safety and Occupational Health Study Section (SOH)
Project Start
1984-01-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1995-03-31
Support Year
8
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Andreoni, K A; Kazui, M; Cameron, D E et al. (1999) Ethane: a marker of lipid peroxidation during cardiopulmonary bypass in humans. Free Radic Biol Med 26:439-45
Risby, T H; Jiang, L; Stoll, S et al. (1999) Breath ethane as a marker of reactive oxygen species during manipulation of diet and oxygen tension in rats. J Appl Physiol 86:617-22
Chin, B Y; Choi, M E; Burdick, M D et al. (1998) Induction of apoptosis by particulate matter: role of TNF-alpha and MAPK. Am J Physiol 275:L942-9
Miller 3rd, E R; Appel, L J; Jiang, L et al. (1997) Association between cigarette smoking and lipid peroxidation in a controlled feeding study. Circulation 96:1097-101
Schwarz, K B; Cox, J M; Sharma, S et al. (1997) Possible antioxidant effect of vitamin A supplementation in premature infants. J Pediatr Gastroenterol Nutr 25:408-14
Foster, W M; Jiang, L; Stetkiewicz, P T et al. (1996) Breath isoprene: temporal changes in respiratory output after exposure to ozone. J Appl Physiol 80:706-10
Risby, T H; Maley, W; Scott, R P et al. (1994) Evidence for free radical-mediated lipid peroxidation at reperfusion of human orthotopic liver transplants. Surgery 115:94-101
Jakab, G J; Risby, T H; Hemenway, D R (1992) Use of physical chemistry and in vivo exposure to investigate the toxicity of formaldehyde bound to carbonaceous particles in the murine lung. Res Rep Health Eff Inst :1-39, discussion 41-9
Jakab, G J; Risby, T H; Sehnert, S S et al. (1990) Suppression of alveolar macrophage membrane-receptor-mediated phagocytosis by model particle-adsorbate complexes: physicochemical moderators of uptake. Environ Health Perspect 89:169-74
Jakab, G J; Risby, T H; Sehnert, S S et al. (1990) Suppression of alveolar macrophage membrane receptor-mediated phagocytosis by model and actual particle-adsorbate complexes. Initial contact with the alveolar macrophage membrane. Environ Health Perspect 86:337-44

Showing the most recent 10 out of 14 publications