Re-evaluation of pulmonary titanium dioxide nanoparticle distribution using the "relative deposition index": Evidence for clearance through microvasculature

ABSTRACT: BACKGROUND: Translocation of nanoparticles (NP) from the pulmonary airways into other pulmonary compartments or the systemic circulation is controversially discussed in the literature. In a previous study it was shown that titanium dioxide (TiO2) NP were "distributed in four lung compartments (air-filled spaces, epithelium/endothelium, connective tissue, capillary lumen) in correlation with compartment size". It was concluded that particles can move freely between these tissue compartments. To analyze whether the distribution of TiO2 NP in the lungs is really random or shows a preferential targeting we applied a newly developed method for comparing NP distributions. METHODS: Rat lungs exposed to an aerosol containing TiO2 NP were prepared for light and electron microscopy at 1 h and at 24 h after exposure. Numbers of TiO2 NP associated with each compartment were counted using energy filtering transmission electron microscopy. Compartment size was estimated by unbiased stereology from systematically sampled light micrographs. Numbers of particles were related to compartment size using a relative deposition index and chi-squared analysis. RESULTS: Nanoparticle distribution within the four compartments was not random at 1 h or at 24 h after exposure. At 1 h the connective tissue was the preferential target of the particles. At 24 h the NP were preferentially located in the capillary lumen. CONCLUSION: We conclude that TiO2 NP do not move freely between pulmonary tissue compartments, although they can pass from one compartment to another with relative ease. The residence time of NP in each tissue compartment of the respiratory system depends on the compartment and the time after exposure. It is suggested that a small fraction of TiO2 NP are rapidly transported from the airway lumen to the connective tissue and subsequently released into the systemic circulation.

Distribution of intracellular and secreted surfactant during postnatal rat lung development

Pulmonary surfactant prevents alveolar collapse via reduction of surface tension. In contrast to human neonates, rats are born with saccular lungs. Therefore, rat lungs serve as a model for investigation of the surfactant system during postnatal alveolar formation. We hypothesized that this process is associated with characteristic structural and biochemical surfactant alterations. We aimed to discriminate changes related to alveolarization from those being either invariable or follow continuous patterns of postnatal changes. Secreted active (mainly tubular myelin (tm)) and inactive (unilamellar vesicles (ulv)) surfactant subtypes as well as intracellular surfactant (lamellar bodies (lb)) in type II pneumocytes (PNII) were quantified before (day (d) 1), during (d 7), at the end of alveolarization (d 14), and after completion of lung maturation (d 42) using electron microscopic methods supplemented by biochemical analyses (phospholipid quantification, immunoblotting for SP-A). Immunoelectron microscopy determined the localization of surfactant protein A (SP-A). (1) At d 1 secreted surfactant was increased relative to d 7-42 and then decreased significantly. (2) Air spaces of neonatal lungs comprised lower fractions of tm and increased ulv, which correlated with low SP-A concentrations in lung lavage fluid (LLF) and increased respiratory rates, respectively. (3) Alveolarization (d 7-14) was associated with decreasing PNII size although volume and sizes of Lb continuously increased. (4) The volume fractions of Lb correlated well with the pool sizes of phospholipids in lavaged lungs. Our study emphasizes differential patterns of developmental changes of the surfactant system relative to postnatal alveolarization.

Characterising the three-dimensional ozone distribution of a tidally locked Earth-like planet

We simulate the 3D ozone distribution of a tidally locked Earth-like exoplanet using the high-resolution, 3D chemistry climate model CESM1(WACCM) and study how the ozone layer of a tidally locked Earth (TLE) (ΩTLE = 1/365 days) differs from that of our present-day Earth (PDE) (ΩPDE = 1/1 day). The middle atmosphere reaches a steady state a symptotically within the first 80 days of the simulation. An upwelling, centred on the subsolar point, is present on the day side while a downwelling, centred on the antisolar point, is present on the night side. In the mesosphere, we find similar global ozone distributions for the TLE and the PDE, with decreased ozone on the day side and enhanced ozone on the night side. In the lower mesosphere, a jet stream transitions into a large-scale vortex around a low-pressure system, located at low latitudes of the TLE night side. In the middle stratosphere, the concentration of odd oxygen is approximately equal to that of the ozone [(Ox) ≈ (O3)]. At these altitudes, the lifetime of odd oxygen is ~16 h and the transport processes significantly contribute to the global distribution of stratospheric ozone. Compared to the PDE, where the strong Coriolis force acts as a mixing barrier between low and high latitudes, the transport processes of the TLE are governed by jet streams variable in the zonal and meridional directions. In the middle stratosphere of the TLE, we find high ozone values on the day side, due to the increased production of atomic oxygen on the day side, where it immediately recombines with molecular oxygen to form ozone. In contrast, the ozone is depleted on the night side, due to changes in the solar radiation distribution and the presence of a downwelling. As a result of the reduced Coriolis force, the tropical and extratropical air masses are well mixed and the global temperature distribution of the TLE stratosphere has smaller horizontal gradients than the PDE. Compared to the PDE, the total ozone column global mean is reduced by ~19.3 %. The day side and the night side total ozone column means are reduced by 23.21 and 15.52 %, respectively. Finally, we present the total ozone column (TOC) maps as viewed by a remote observer for four phases of the TLE during its revolution around the star. The mean TOC values of the four phases of the TLE vary by up to 23 %.