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SOLUBLE COMPONENTS OF UTAH VALLEY PARTICULATE POLLUTION ALTER ALVEOLAR MACROPHAGE FUNCTION IN VIVO AND IN VITRO
Soukup, J M., A. J. Ghio, AND S E. Becker. SOLUBLE COMPONENTS OF UTAH VALLEY PARTICULATE POLLUTION ALTER ALVEOLAR MACROPHAGE FUNCTION IN VIVO AND IN VITRO. INHALATION TOXICOLOGY 12(5):401-414.
Water-soluble extracts of Utah Valley dust (UVD) have been found to cause inflammatory injury of the lung in both humans and rodents. The degree of lung damage found correlated with the metal content in the extracts. In the present study, extracts of a set of UVD PM(10) filters collected over a 3-yr span, varying in total metal content with yr 1 = yr 3 > yr 2, were used to assess effects on human alveolar macrophage (AM) function. The phagocytic activity and oxidative response of AM was investigated 24 h after segmental instillation of UVD, or after overnight in vitro culture of the extracts with AM. Using flow cytometry analysis, AM phagocytosis of fluorescently (FITC)-labeled Saccharomyces cerevisiae was inhibited following instillation of UVD1 (61%) but not by yr 2 and 3. Neither baseline oxidant activity nor phorbol ester-induced oxidant generation was affected by the dust extracts in vivo. Overnight culture of AM with UVD1 resulted in a significant decrease in the percentage of AM phagocytizing particles (30%), while no significant effect on this function was found with the other two extracts. Furthermore, only UVD1 caused an immediate oxidative response in AM, although both UVD1 and UVD3 inhibited oxidant activity in AM when the cells were incubated with the extracts overnight. The detrimental effects on AM host defenses could be due to apoptosis, which was evident in cells exposed to the UVD1 and to a much lesser extent with AM exposed to yr 2 and 3. The component(s) responsible for the toxic effects on AM in vitro were removed by pretreatment of the UVD extracts with a polycation chelating resin, chelex-100. However, since yr 1 and 3 are similar in their soluble metal content, but differ in their effects on AM phagocytosis, it is possible that the metals may not be the culprit in effects of particulate matter on AM host defense.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
HUMAN STUDIES DIVISION
CLINICAL RESEARCH BRANCH