The effects of PM10 particles and oxidative stress on macrophages and lung epithelial cells:: modulating effects of calcium-signaling antagonists

We have previously examined the ability of air pollution particles ( PM10) to promote release of the proinflammatory cytokine tumor necrosis factor-alpha ( TNF-alpha) from human peripheral blood mononuclear cells and demonstrated a role for calcium as a signaling molecule in this process. We have now studied the ability of oxidative stress induced by a synthetic oxidant tert- butyl hydroperoxide ( tBHP) to induce TNF-alpha production via calcium signaling in the mouse macrophage cell line ( J774). The oxidant tBHP significantly increased intracellular calcium and the release of TNF-alpha in J774 cells, an effect that was reduced to control levels by inhibition of calcium signaling with verapamil, BAPTA-AM, and W-7. This study also investigated interactions between PM10-treated macrophages and epithelial cells by using conditioned medium ( CM) from PM10-treated mononuclear cells to stimulate the release of the neutrophil chemoattractant chemokine IL-8 from A549 lung epithelial cells. TNF-alpha protein release was demonstrated in human mononuclear cells after PM10 treatment, an effect that was inhibited by calcium antagonists. Treatment of A549 cells with monocyte/ PM10 CM produced increased IL- 8 release that was reduced with CM from monocyte/ PM10/ calcium antagonist treatments. The expression of ICAM- 1 was increased after incubation with CM from monocyte/ PM10 treatment, and this increase was prevented by treatment with CM from monocyte/ PM10/ calcium antagonist. These data demonstrate a link between oxidative stress, calcium, and inflammatory mediator production in macrophages and lung epithelial cells.