Environmental Health Perspectives 105, Supplement 5, September 1997

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Bioavailable Transition Metals in Particulate Matter Mediate Cardiopulmonary Injury in Healthy and Compromised Animal Models

Daniel L. Costa and Kevin L. Dreher

Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina

Abstract
Many epidemiologic reports associate ambient levels of particulate matter (PM) with human mortality and morbidity, particularly in people with preexisting cardiopulmonary disease (e.g., chronic obstructive pulmonary disease, infection, asthma). Because much ambient PM is derived from combustion sources, we tested the hypothesis that the health effects of PM arise from anthropogenic PM that contains bioavailable transition metals. The PM samples studied derived from three emission sources (two oil and one coal fly ash) and four ambient airsheds (St. Louis, MO; Washington; Dusseldorf, Germany; and Ottawa, Canada). PM was administered to rats by intratracheal instillation in equimass or equimetal doses to address directly the influence of PM mass versus metal content on acute lung injury and inflammation. Our results indicated that the lung dose of bioavailable transition metal, not instilled PM mass, was the primary determinant of the acute inflammatory response for both the combustion source and ambient PM samples. Residual oil fly ash, a combustion PM rich in bioavailable metal, was evaluated in a rat model of cardiopulmonary disease (pulmonary vasculitis/hypertension) to ascertain whether the disease state augmented sensitivity to that PM. Significant mortality and enhanced airway responsiveness were observed. Analysis of the lavaged lung fluids suggested that the milieu of the inflamed lung amplified metal-mediated oxidant chemistry to jeopardize the compromised cardiopulmonary system. We propose that soluble metals from PM mediate the array of PM-associated injuries to the cardiopulmonary system of the healthy and at-risk compromised host. -- Environ Health Perspect 105(Suppl 5):1053-1060 (1997)

Key words : particulate matter, metals, air pollution, lung injury, animal models, pulmonary hypertension

This paper is based on a presentation at The Sixth International Meeting on the Toxicology of Natural and Man-Made Fibrous and Non-Fibrous Particles held 15-18 September 1996 in Lake Placid, New York. Manuscript received at EHP 26 March 1997; accepted 17 July 1997.
The authors acknowledge the contributions of the staff of the Pulmonary Toxicology Branch in this research effort and the assistance of D. Doerfler with the statistical analyses. In addition, the authors thank L. Folinsbee and L. Birnbaum for their constructive critiques of this manuscript. This manuscript has been reviewed and approved for publication by the NHEERL. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.
Address correspondence to Dr. D.L. Costa, Pulmonary Toxicology Branch, MD-82, National Health and Environmental Effects Research Laboratory; U.S. Environmental Protection Agency, ERC Building, Research Triangle Park, NC 27711. Telephone: (919) 541-2531. Fax: (919) 541-0026. E-mail: costa.dan@epamail.epa.gov
Abbreviations used: BAL, bronchoalveolar lavage; CFA, coal fly ash; DC, Washington; DOFA, fly ash from a domestic oil-burning furnace; Dus, Dusseldorf, Germany; IT, intratracheal; LDH, lactate dehydrogenase; MCT, monocrotaline; NIST, National Institute of Standards and Technology; Ott, Ottawa, Ontario, Canada; PM, particulate matter; PM 10 , particulate matterLess than or = to10µm in aerodynamic diameter; PMN, polymorphonuclear neutrophil; ROFA, residual oil fly ash; St.L, St. Louis, MO; TSP, total suspended particulates; U.S. EPA, U.S. Environmental Protection Agency.

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Last Update: October 17, 1997