Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells

Abstract

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 μm). 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 μm) 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.

Effect of Polycyclic Aromatic Hydrocarbons and Carbon Black Particles on Pro-Inflammatory Cytokine Secretion: Impact of PAH Coating Onto Particles

“…Fine particles (like CB) penetrate into cells by an endocytic process; however, the mechanism of ufCB uptake is still under debate. Results reported by Geiser et al (2005) suggested a mechanism that did not rely upon vesicle formation or an actin-based mechanism. As a consequence, the bioavailability of pollutants adsorbed onto particles of differing sizes must likely be different.…”

“…The size of particles determines the penetration into the cells (Geiser et al, 2005). Fine particles (like CB) penetrate into cells by an endocytic process; however, the mechanism of ufCB uptake is still under debate.…”

Carbon nanoparticle-induced lung epithelial cell proliferation is mediated by receptor-dependent Akt activation

“…The involvement of integrins suggests a potential of outside-in signaling following an interaction of the particles with extracellular structures of the membrane. However, nanoparticles have been described to enter the cell easily without using specific uptake mechanisms (16). It therefore may be speculated that the activation of the described pathway is triggered by intracellular processes comparable with the phosphorylation of EGF-R by intracellularly generated reactive oxygen species (32).…”

Use of Nanoparticles in Swiss Industry: A Targeted Survey

“…Nanosized particles are suspected to enter the human cells more easily than microsized particles (7), and ambient air-pollution particles smaller than 2.5 µm (PM2.5) have already been shown to be harmful to human health (8)(9)(10). The surface-to-volume ratio of nanoparticles is large, which may explain their high biological activity.…”