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 (PM(10)) 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 PM(10)-treated macrophages and epithelial cells by using conditioned medium (CM) from PM(10)-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 PM(10) treatment, an effect that was inhibited by calcium antagonists. Treatment of A549 cells with monocyte/PM(10) CM produced increased IL-8 release that was reduced with CM from monocyte/PM(10)/calcium antagonist treatments. The expression of ICAM-1 was increased after incubation with CM from monocyte/PM(10) treatment, and this increase was prevented by treatment with CM from monocyte/PM(10)/calcium antagonist. These data demonstrate a link between oxidative stress, calcium, and inflammatory mediator production in macrophages and lung epithelial cells.