Macrophage-derived exosomal TNF-α promotes pulmonary surfactant protein expression in PM2.5-induced acute lung injury.

Short-term high-concentration exposure to airborne fine particulate matter (PM2.5) is strongly associated with the risk of acute lung injury (ALI). It has been recently reported that exosomes (Exos) involve in the progression of respiratory diseases. However, the molecular mechanisms by which exosome-mediated intercellular signaling exacerbate PM2.5-induced ALI remains largely unaddressed. In the present study, we firstly investigated the effect of macrophage-derived exosomal tumor necrosis factor α (TNF-α) on pulmonary surfactant proteins (SPs) expression in epithelial MLE-12 cells after PM2.5 exposure. The higher levels of exosomes in the bronchoalveolar lavage fluid (BALF) of PM2.5-induced ALI mice were found. BALF-exosomes significantly up-regulated SPs expression in MLE-12 cells. Moreover, we found that remarkably high expression of TNF-α in exosomes secreted by PM2.5-treated RAW264.7 cells. Exosomal TNF-α promoted thyroid transcription factor-1 (TTF-1) activation and SPs expression in MLE-12 cells. Furthermore, intratracheal instillation of macrophage-derived TNF-α-containing exosomes increased epithelial cell SPs expression in the lungs of mice. Taken together, these results suggest that macrophages-secreted exosomal TNF-α can trigger epithelial cell SPs expression, which provides new insight and potential target in the mechanism of epithelial cell dysfunction in PM2.5-induced ALI.

Interaction of industrial smelting soot particles with pulmonary surfactant: Pulmonary toxicity of heavy metal-rich particles.

Inhalable particles can influence the interfacial behavior of pulmonary surfactant (PS) resulting in various pulmonary diseases. However, the effects of actually airborne particles on the interfacial behavior of PS and its role in the alteration for soluble metal fraction in particles are entirely unexplored. Herein, we investigated the interaction of PS extracted from porcine lungs with smelting soot fine particles as a model of inhaled heavy metal-rich particles. Our results showed that the phase behavior and foamability of PS were obviously altered in the presence of smelting soot fine particles. In addition, the soluble heavy metals in smelting soot fine particles notably increased in the presence of PS as compared to that of saline solution. Further experiments conducted by adding PS's major components (dipalmitoylphosphatidylcholine, DPPC; bovine serum albumin, BSA) demonstrated that comparison of DPPC, adsorbed BSA is beneficial for the dissolution of heavy metals in smelting soot fine particles. Dynamic light scattering experiments verified that the well dispersion of smelting soot fine particles in the presence of BSA may be responsible for the higher solubility of heavy metals. These findings indicate that PS's interfacial behavior change and PS-enhanced solubilization release of metal components may increase the potentially pulmonary risk in the exposure of airborne fine particles enriched with heavy metals.

Response surface methodological (RSM) approach for optimizing the removal of trihalomethanes (THMs) and its precursor's by surfactant modified magnetic nanoadsorbents (sMNP) - An endeavor to diminish probable cancer risk.

Response surface methodology (RSM) approach was used for optimization of the process parameters and identifying the optimal conditions for the removal of both trihalomethanes (THMs) and natural organic matter (NOM) in drinking water supplies. Co-precipitation process was employed for the synthesis of magnetic nano-adsorbent (sMNP), and were characterized by field emission scanning electron microscopy (SEM), trans-emission electron microscopy (TEM), BET (Brunauer-Emmett-Teller), energy dispersive X-ray (EDX) and zeta potential. Box-Behnken experimental design combined with response surface and optimization was used to predict THM and NOM in drinking water supplies. Variables were concentration of sMNP (0.1 g to 5 g), pH (4-10) and reaction time (5 min to 90 min). Statistical analysis of variance (ANOVA) was carried out to identify the adequacy of the developed model, and revealed good agreement between the experimental data and proposed model. The experimentally derived RSM model was validated using t-test and a range of statistical parameters. The observed R2 value, adj. R2, pred. R2 and "F-values" indicates that the developed THM and NOM models are significant. Risk analysis study revealed that under the RSM optimized conditions, a marked reduction in the cancer risk of THMs was observed for both the groups studied. Therefore, the study observed that the developed process and models can be efficiently applied for the removal of both THM and NOM from drinking water supplies.

Polymer-Lipid Microparticles for Pulmonary Delivery.

Toward engineering approaches that are designed to optimize the particle size, morphology, and mucoadhesion behavior of the particulate component of inhaler formulations, this paper presents the preparation, physicochemical characterization, and preliminary in vitro evaluation of multicomponent polymer-lipid systems that are based on "spray-drying engineered" α-lactose monohydrate microparticles. The formulations combine an active (budesonide) with a lung surfactant (dipalmitoylphosphatidylcholine) and with materials that are known for their desirable effects on morphology (polyvinyl alcohol), aerosolization (l-leucine), and mucoadhesion (chitosan). The effect of the composition of formulations on the morphology, distribution, and in vitro mucoadhesion profiles is presented along with "Calu-3 cell monolayers" data that indicate good cytocompatibility and also with simulated-lung-fluid data that are consistent with the therapeutically useful release of budesonide.

Lysis of red blood cells and alveolar epithelial toxicity by therapeutic pulmonary surfactants.

The risk of pulmonary hemorrhage is increased in extremely low birth weight infants treated with surfactant. The pathogenesis of this increased risk is far from clear. We tested whether exposure of cell membranes to surfactant may lead to increased membrane permeability, hypothesizing that this process may contribute to the occurrence of alveolar hemorrhage after surfactant treatment. Aliquots of washed packed red blood cells (used as membrane model) were suspended in 0.9% NaCl with various concentrations of Survanta or Exosurf for either 2 or 24 h at 37 degrees C. Cytolysis was measured by spectrophotometric determination of free Hb after centrifugation. Red cells suspended in 0.9% NaCl alone, distilled water, or various concentrations of melittin were used as negative and positive controls. Both surfactants were associated with increased hemolysis to 35% of maximum at concentrations of 1.25 mg/2 mL. Above these concentrations, Survanta was associated with no increase in hemolysis, whereas Exosurf increased hemolysis to 60% of maximum at concentrations of 12.5 mg/2 mL. In additional experiments, primary cultures of alveolar type II cells from adult rats were treated with Survanta, Exosurf, the Exosurf components tyloxapol and hexadecanol, melittin, or culture medium alone. After 24 h of incubation, lactate dehydrogenase release into the media was measured as a percent of total lactate dehydrogenase activity to indicate cytotoxicity. Lactate dehydrogenase release was < 10% for control experiments but increased sharply with Exosurf and its components tyloxapol and hexadecanol. These results indicate that surfactant may be associated with in vitro cytotoxicity and that this property differs for different surfactants and different dosages.