Distribution pattern of inhaled ultrafine gold particles in the rat lung.
The role of alveolar macrophages in the fate of ultrafine particles in the lung was investigated. Male Wistar-Kyoto rats were exposed to ultrafine gold particles, generated by a spark generator, for 6 h at a concentration of 88 microg/m3 (4 x 10(6)/cm3, 16 nm modal mobility diameter). Up to 7 days, the animals were serially sacrificed, and lavaged cells and lung tissues were examined by transmission electron microscopy. The gold concentration/content in the lung, lavage fluid, and blood was estimated by inductively coupled plasma-mass spectrometry. Gold particles used were spherical and electron dense with diameters of 5-8 nm. The particles were individual or slightly agglomerated. By inductively coupled plasma-mass spectrometry analysis of the lung, 1945 +/- 57 ng (mean +/- SD) and 1512 +/- 184 ng of gold were detected on day 0 and on day 7, respectively, indicating that a large portion of the deposited gold particles was retained in the lung tissue. In the lavage fluid, 573 +/- 67 ng and 96 +/- 29 ng were found on day 0 and day 7, respectively, which means that 29% and 6% of the retained gold particles were lavageable on these days. A low but significant increase of gold (0.03 to 0.06% of lung concentration) was found in the blood. Small vesicles containing gold particles were found in the cytoplasm of alveolar macrophages. In the alveolar septum, the gold particles were enclosed in vesicles observed in the cytoplasm of alveolar type I epithelial cells. These results indicate that inhaled ultrafine gold particles in alveolar macrophages and type I epithelial cells are processed by endocytotic pathways, though the uptake of the gold particles by alveolar macrophages is limited. To a low degree, systemic particle translocation took place.
Takenaka
S
S
GSF-Institute for Inhalation Biology, Neuherberg/Munich, Germany. takenaka@gsf.de
Karg
E
E
Kreyling
W G
WG
Lentner
B
B
Möller
W
W
Behnke-Semmler
M
M
Jennen
L
L
Walch
A
A
Michalke
B
B
Schramel
P
P
Heyder
J
J
Schulz
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004705:Endocytosis; D006046:Gold / Q000737:chemistry / Q000493:pharmacokinetics*; D019570:Inhalation Exposure; D008168:Lung / Q000378:metabolism* / Q000648:ultrastructure; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D051381:Rats; D011921:Rats, Inbred WKY; D020545:Respiratory Mucosa / Q000378:metabolism / Q000648:ultrastructure
D006046:Gold