US EPA

87362 

Journal Article 

Ultrafine particles cross cellular membranes by nonphagocytic mechanisms in lungs and in cultured cells 

Geiser, M; Rothen-Rutishauser, B; Kapp, N; Schurch, S; Kreyling, W; Schulz, H; Semmler, M; Im Hof, V; Heyder, J; Gehr, P 

2005 

Yes 

Environmental Health Perspectives
ISSN: 0091-6765
EISSN: 1552-9924 

113 

11 

1555-1560 

English 

16263511 

10.1289/ehp.8006 

WOS:000232916700038 

High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPs; particles < 0.1 Ám). Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 Ám) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential. 

aerosol; erythrocytes; lungs; macrophages; microscopy; nanoparticles; rats; surfactant