Soluble components of Utah Valley particulate pollution alter alveolar macrophage function in vivo and in vitro

Water-soluble extracts of Utah Valley dust (UVD) have been found to cause i nflammatory injury of the lung in both humans and rodents. The degree of lu ng damage found correlated with the metal content in the extracts. In the p resent study, extracts of a set of UVD PM10 filters collected over a 3-yr s pan, varying in total metal content with yr 1 = yr 3 > yr 2, were used to a ssess effects on human alveolar macrophage (AM) function. The phagocytic ac tivity and oxidative response of AM was investigated 24 h after segmental i nstillation of UVD, or after overnight in vitro culture of the extracts wit h AM. Using flow cytometry analysis, AM phagocytosis of fluorescently (FITC )-labeled Saccharomyces cerevisiae war inhibited following instillation of UVD1 (61%) but not by)yr 2 and 3. Neither baseline oxidant activity nor pho rbol 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 UVD 1 and UVD3 inhibited oxidant activity in AM when the cells were incubated w ith the extracts overnight. The detrimental effects on AM host defenses cou ld 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) res ponsible for the toxic effects on AM in vitro were removed by pretreatment of the UVD extracts with a polycation chelating resin, chelex-100. Hort ev er, since yr 1 and 3 are similar in their soluble metal content, but differ in their effects on AM phagocytosis, ii is possible that the metals may no t be the culprit in effects of particulate matter on AM host defense.