Mechanisms of particle-induced activation of alveolar macrophages.
Bovine alveolar macrophages were exposed in vitro to quartz dusts, metal-containing dusts or silica particles coated with a single metal oxide. The release of reactive oxygen intermediates (ROI) was measured in short-term incubations (90 min). The secretion of both ROI was markedly enhanced by silica particles coated with vanadium oxide and lowered by copper oxide-coated particles. The particle-induced ROI release was significantly decreased by the inhibition of protein kinase C (PKC) as well as phospholipase A2, suggesting the involvement of both enzymes in the NADPH oxidase activation. Quartz dusts induced a transient increase of free cytosolic calcium ion concentration, slight intracellular acidification, and depolarization of the plasma membrane. In the presence of EGTA or verapamil the rise of [Ca2+]i was diminished, suggesting an influx of extracellular calcium ions. The PKC inhibitor GF 109203X did not inhibit the quartz-induced calcium rise, while both the cytosolic acidification and depolarization were prevented. BSA-coating of the quartz particles abolished the calcium influx as well as the decrease of pHi, and possibly hyperpolarized the plasma membrane.
Gercken
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Department of Biochemistry and Molecular Biology, University of Hamburg, Germany.
Berg
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Dörger
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Schlüter
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D000818:Animals; D002118:Calcium / Q000032:analysis; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D004391:Dust / Q000009:adverse effects*; D005434:Flow Cytometry / Q000379:methods; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008262:Macrophage Activation / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D019216:Metals, Heavy / Q000494:pharmacology; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000187:drug effects; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000187:drug effects; D011791:Quartz / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D004391:Dust; D019216:Metals, Heavy; D017382:Reactive Oxygen Species; D013481:Superoxides; D011791:Quartz; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium