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In spite of the considerable efforts invested to understand the environmental health and safety (EHS) impacts of ultrafine particles, such as the representative PM2.5, there are still significant knowledge gaps to be filled. No conclusive understandings have been obtained about the physicochemical determinants in accounting for differential adverse outcomes. Here we compared the cytotoxicity of four carbon black (CB) particles with similar physicochemical properties except for their oxygen contents (C824455 < C1864 < Printex U < SB4A). We found that these four CB particles manifested in vitro and in vivo cytotoxicity reversely related to their oxygen contents, namely a hierarchy of cytotoxicity: C824455 > C1864 > Printex U > SB4A. Among these CB particles, the most significant lung injury (e.g. collapses and inflammation) and macrophagic activation were found for C824455 and C1864, in particular for C824455. All these differences in toxicity profiles, including in vitro and in vivo cytotoxicity, pro-inflammatory effects and direct damages to the lung epithelia, should be (at least partially) ascribed to the oxygen content in these CB particles that in turn determined their transformation, i.e. the different aggregation states. Nonetheless, PM2.5 likewise caused severe in vivo and in vitro toxicities to the lung cells and macrophages. This study thus offers more insights into the structure-activity relationship (SAR) and opens a new avenue to elucidate the physicochemical determinants in evoking lung injuries by ultrafine airborne particles., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Environmental exposure and health risk upon engineered nanomaterials are increasingly concerned. The family of mesoporous carbon nanomaterials (MCNs) is a rising star in nanotechnology for multidisciplinary research with versatile applications in electronics, energy and gas storage, and biomedicine. Meanwhile, there is mounting concern on their environmental health risks due to the growing production and usage of MCNs. The lung is the primary site for particle invasion under environmental exposure to nanomaterials. Here, we studied the comprehensive toxicological profile of MCNs in the lung under the scenario of moderate environmental exposure. It was found that at a low concentration of 10μg/mL MCNs induced biophysical inhibition of natural pulmonary surfactant. Moreover, MCNs at similar concentrations reduced viability of J774A.1 macrophages and lung epithelial A549 cells. Incubating with nature pulmonary surfactant effectively reduced the cytotoxicity of MCNs. Regarding the pro-inflammatory responses, MCNs activated macrophages in vitro, and stimulated lung inflammation in mice after inhalation exposure, associated with lung fibrosis. Moreover, we found that the size of MCNs played a significant role in regulating cytotoxicity and pro-inflammatory potential of this nanomaterial. In general, larger MCNs induced more pronounced cytotoxic and pro-inflammatory effects than their smaller counterparts. Our results provided valuable information on the toxicological profile and environmental health risks of MCNs, and suggested that fine-tuning the size of MCNs could be a practical precautionary design strategy to increase safety and biocompatibility of this nanomaterial., (Copyright © 2017. Published by Elsevier B.V.)

The role of mitochondrial energy metabolism in maintaining lung function is not understood. We previously observed reduced lung function in mice lacking the fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase (LCAD). Here, we demonstrate that long-chain acylcarnitines, a class of lipids secreted by mitochondria when metabolism is inhibited, accumulate at the air-fluid interface in LCAD(-/-) lungs. Acylcarnitine accumulation is exacerbated by stress such as influenza infection or by dietary supplementation with l-carnitine. Long-chain acylcarnitines co-localize with pulmonary surfactant, a unique film of phospholipids and proteins that reduces surface tension and prevents alveolar collapse during breathing. In vitro, the long-chain species palmitoylcarnitine directly inhibits the surface adsorption of pulmonary surfactant as well as its ability to reduce surface tension. Treatment of LCAD(-/-) mice with mildronate, a drug that inhibits carnitine synthesis, eliminates acylcarnitines and improves lung function. Finally, acylcarnitines are detectable in normal human lavage fluid. Thus, long-chain acylcarnitines may represent a risk factor for lung injury in humans with dysfunctional fatty acid oxidation., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Pulmonary surfactant facilitates breathing by forming a surface tension reducing film at the air-liquid interface of the alveoli. The objective was to characterize the structure of surfactant films using endogenous rat surfactant. Solid-support surfactant films, at different surface pressures, were obtained using a Langmuir balance and were analyzed using atomic force microscopy. The results showed a lipid film structure with three distinct phases: liquid expanded, liquid ordered and liquid condensed. The area covered by the liquid condensed domains increased as surface pressure increased. The presence of liquid ordered phase within these structures correlated with the cholesterol content. At a surface pressure of 50 mN/m, stacks of bilayers appeared. Several structural details of these films differ from previous observations made with goat and exogenous surfactants. Overall, the data indicate that surfactant films demonstrate phase separation at low surface pressures and multilayer formation at higher pressure, features likely important for normal surfactant function., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The surface activity of bovine lipid extracted surfactant (BLES) preparations used in surfactant replacement therapy is studied in dynamic film compression/expansion cycles as a function of relative humidity, surfactant concentration, compression rate, and compression periodicity. BLES droplets were formed in a constrained sessile droplet configuration (CSD). Images obtained during cycling were analyzed using axisymmetric drop shape analysis (ADSA) to yield surface tension, surface area, and drop volume data. The experiments were conducted in a chamber that allowed both humid (100% RH), and "dry" air (i.e. less than 20% RH) environments. It was observed that in humid environments BLES films are not stable and tend to have poor surface activity compared to BLES films exposed to dry air. Further analysis of the data reveal that if BLES films are compressed fast enough (i.e. at physiological conditions) to avoid film hydration, lower minimum surface tensions are achieved. A film hydration-relaxation mechanism is proposed to explain these observations.

In the lungs, oxygen transfer from the inspired air to the capillary blood needs to cross the surfactant lining layer of the alveoli. Therefore, the gas transfer characteristics of lung surfactant film are of fundamental physiological interest. However, previous in vitro studies-most relied on the Langmuir-type balance-fail to cover the low surface tension range (i.e., less than the equilibrium surface tension of approximately 25 mJ/m2) due to film leakage. We have recently developed a novel in vitro experimental strategy, the combination of axisymmetric drop shape analysis and captive bubble technique (ADSA-CB), in studying the effect of surfactant films on interfacial gas transfer (Langmuir 2005, 21, 5446). In the present work, ADSA-CB is used as a micro-film-balance to study the effect of compressed bovine lipid extract surfactant (BLES) films on oxygen transfer. A low surface tension ranging from approximately 25 mJ/m2 to 2 mJ/m2 is studied. The experimental results suggest that lung surfactant films at a low surface tension near 2 mJ/m2 provide resistance to oxygen transfer, as indicated by a decrease of 30-50% in the mass transfer coefficient (kL) of oxygen in BLES suspensions with respect to water. At higher surface tension (i.e., >6 mJ/m2), the resistance to oxygen transfer is only modest, i.e., the decrease in kL is less than 20% compared to water. The experimental results suggest that lung surfactant plays a role in oxygen transfer in the pulmonary system.