Oxidative stress and lipid mediators induced in alveolar macrophages by ultrafine particles.
In ambient aerosols, ultrafine particles (UFP) and their agglomerates are considered to be major factors contributing to adverse health effects. Reactivity of agglomerated UFP of elemental carbon (EC), Printex 90, Printex G, and diesel exhaust particles (DEP) was evaluated by the capacity of particles to oxidize methionine in a cell-free in vitro system for determination of their innate oxidative potential and by alveolar macrophages (AMs) to determine production of arachidonic acid (AA), including formation of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), reactive oxygen species (ROS), and oxidative stress marker 8-isoprostane. EC exhibiting high oxidative potential induced generation of AA, PGE2, LTB4, and 8-isoprostane in canine and human AMs. Printex 90, Printex G, and DEP, showing low oxidative capacity, still induced formation of AA and PGE2, but not that of LTB4 or 8-isoprostane. Aging of EC lowered oxidative potential while still inducing production of AA and PGE2 but not that of LTB4 and 8-isoprostane. Cellular ROS production was stimulated by all particles independent of oxidative potential. Particle-induced formation of AA metabolites and ROS was dependent on mitogen-activated protein kinase kinase 1 activation of cytosolic phospholipase A2 (cPLA2) as shown by inhibitor studies. In conclusion, cPLA2, PGE2, and ROS formation was activated by all particle types, whereas LTB4 production and 8-isoprostane were strongly dependent on particles' oxidative potential. Physical and chemical parameters of particle surface correlated with oxidative potential and stimulation of AM PGE2 and 8-isoprostane production.
Beck-Speier
Ingrid
I
GSF-National Research Center for Environment and Health, Institute for Inhalation Biology, D-85758 Neuherberg/Munich, Germany. beck-speier@gsf.de
Dayal
Niru
N
Karg
Erwin
E
Maier
Konrad L
KL
Schumann
Gabriele
G
Schulz
Holger
H
Semmler
Manuela
M
Takenaka
Shinji
S
Stettmaier
Kurt
K
Bors
Wolf
W
Ghio
Andy
A
Samet
James M
JM
Heyder
Joachim
J
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004285:Dogs; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D050356:Lipid Metabolism; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D018384:Oxidative Stress; D010587:Phagocytosis; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D017382:Reactive Oxygen Species
D017382:Reactive Oxygen Species; D010741:Phospholipases A; D054467:Phospholipases A2