The effect of titanium dioxide nanoparticles on pulmonary surfactant function and ultrastructure.
BACKGROUND
Pulmonary surfactant reduces surface tension and is present at the air-liquid interface in the alveoli where inhaled nanoparticles preferentially deposit. We investigated the effect of titanium dioxide (TiO(2)) nanosized particles (NSP) and microsized particles (MSP) on biophysical surfactant function after direct particle contact and after surface area cycling in vitro. In addition, TiO(2) effects on surfactant ultrastructure were visualized.


METHODS
A natural porcine surfactant preparation was incubated with increasing concentrations (50-500 microg/ml) of TiO(2) NSP or MSP, respectively. Biophysical surfactant function was measured in a pulsating bubble surfactometer before and after surface area cycling. Furthermore, surfactant ultrastructure was evaluated with a transmission electron microscope.


RESULTS
TiO(2) NSP, but not MSP, induced a surfactant dysfunction. For TiO(2) NSP, adsorption surface tension (gammaads) increased in a dose-dependent manner from 28.2 + or - 2.3 mN/m to 33.2 + or - 2.3 mN/m (p < 0.01), and surface tension at minimum bubble size (gammamin) slightly increased from 4.8 + or - 0.5 mN/m up to 8.4 + or - 1.3 mN/m (p < 0.01) at high TiO(2) NSP concentrations. Presence of NSP during surface area cycling caused large and significant increases in both gammaads (63.6 + or - 0.4 mN/m) and gammamin (21.1 + or - 0.4 mN/m). Interestingly, TiO(2) NSP induced aberrations in the surfactant ultrastructure. Lamellar body like structures were deformed and decreased in size. In addition, unilamellar vesicles were formed. Particle aggregates were found between single lamellae.


CONCLUSIONS
TiO(2) nanosized particles can alter the structure and function of pulmonary surfactant. Particle size and surface area respectively play a critical role for the biophysical surfactant response in the lung.
Fraunhofer Institute of Toxicology and Experimental Medicine, Division of Immunology, Allergology and Airway Research, Nikolai-Fuchs-Str, 1, 30625 Hannover, Germany. carsten.schleh@item.fraunhofer.de
Carsten
C
Schleh
Christian
C
Mühlfeld
Karin
K
Pulskamp
Andreas
A
Schmiedl
Matthias
M
Nassimi
Hans D
HD
Lauenstein
Armin
A
Braun
Norbert
N
Krug
Veit J
VJ
Erpenbeck
Jens M
JM
Hohlfeld
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D019570:Inhalation Exposure; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D037661:Pulmonary Surfactant-Associated Proteins / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011791:Quartz / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013500:Surface Tension; D013552:Swine; D014025:Titanium / Q000494:pharmacology*; D014463:Ultrasonography
D037661:Pulmonary Surfactant-Associated Proteins; D011791:Quartz; C009495:titanium dioxide; D014025:Titanium