MECHANISMS OF PARTICLE-INDUCED ACTIVATION OF ALVEOLAR MACROPHAGES

Bovine alveolar macrophages were exposed in vitro to quartz dusts, met al-containing dusts or silica particles coated with a single metal oxi de. The release of reactive oxygen intermediates (ROI) was measured in short-term incubations (90 min). The secretion of both ROI was marked ly enhanced by silica particles coated with vanadium oxide and lowered by copper oxide-coated particles. The particle-induced ROI release wa s significantly decreased by the inhibition of protein kinase C (PKC) as well as phospholipase A(2), suggesting the involvement of both enzy mes in the NADPH oxidase activation. Quartz dusts induced a transient increase of free cytosolic calcium ion concentration, slight intracell ular acidification, and depolarization of the plasma membrane. In the presence of EGTA or verapamil the rise of [Ca2+](i) was diminished, su ggesting an influx of extracellular calcium ions. The PKC inhibitor GF 109203X did not inhibit the quartz-induced calcium rise, while both t he cytosolic acidification and depolarization were prevented. BSA-coat ing of the quartz particles abolished the calcium influx as well as th e decrease of pH(i), and possibly hyperpolarized the plasma membrane.