Reactions of macrophages exposed to particles <10 microm

This study describes experiments on cytotoxic effects and the production of oxidative radicals and the proinflammatory cytokine tumor growth factor alpha (TNFalpha) in a cell line of rat lung macrophages exposed to aqueous extracts from ambient air particles <10 microm (PM(10)) collected on Teflon filters. The particles were collected during the four seasons at two urban sites, one rural site, and one alpine site in Switzerland. Cytotoxic effects, determined as a reduction in the metabolic activity, were found in particle extracts from all sites and seasons. Taking together the data from all sites and seasons, a dose-response function was observed between the particle mass on the filter and toxicity (r(2)=0.633, linear regression). The release of the pro-inflammatory cytokine TNFalpha as well as of oxidative radicals was most pronounced in particles collected in spring-summer and autumn. While at Montana (alpine), the stimulation of the cells was positively correlated with the particle mass on the filters, this correlation was negative at the urban sites Zürich and Lugano. It is interpreted that at high PM(10) levels, as in these cities, macrophages are inhibited by increasing air pollution due to toxic effects. Cytotoxic effects and the release of oxidative radicals could be inhibited when the extracts were treated with an endotoxin-neutralizing protein. This suggests that endotoxin, a cell-wall constituent of gram-negative bacteria, is one of the factors which modulates macrophage activity. All together, the experiments indicate that in the PM(10) fraction, water-soluble macrophage-toxic and macrophage-stimulating compounds are present. The data offer an explanation for at least some of the known harmful effects of PM(10), and confirm endotoxin as a possible reactant.