Behaviors Of Atmospheric Fine Particulate Matters In Simulated Lung Fluid, Their Effects On Model Cell Membranes And Cytotoxicity

With the development of industry and the advancement of urbanization, haze has been one of the major problems of environmental pollution in China, threatening public health. Atmospheric particulate matter (PM) is culprit of haze while fine particulate matter (PM2.5) accounts for the largest. PM2.5 can go directly to the alveoli of the lungs as the aerodynamic equivalent diameter< 2.5 μm. They can go through multilayer barriers of the respiratory system and even blood-air barrier, then arrive at remote organs and harm human health. In the past few decades, the health effects and cytotoxicity of PM2.5 have been extensively studied. PM2.5 has carcinogenicity, mutagenicity and genotoxicity, can cause inflammation, oxidative damage and DNA damage, and may trigger pulmonary disease, cardiovascular disease, nervous system disease or even cancer. However, the bio-availability research of PM2.5 is not comprehensive. The aggregation and sedimentation processes of PM2.5 in lung fluid and their heath effect are not well known. The mechanisms of PM2.5-induced cell membrane damage and its relationship with cytotoxicity are unclear. There is no reliable research on the cytotoxic effects of different fraction of PM2.5.In this study, we collected PM2.5 in Jinan and analyzed its main components. Agglomeration and sedimentation performances of PM2.5 have been investigated in lung fluid using simulated lung fluid (SLF). The effects of PM2.5 on cell membranes have been studied through model membranes. We also separated the soluble and insoluble fraction of PM2.5, studied their cytotoxicity on human lung adenocarcinoma A549 cells and discussed the mechanism of PM2.5 to harm human body after inhalation into lung. The concrete results are as following:(1) Organic acids, NR4+, SO42-, NO3- were detected in PM2.5 soluble fraction. The insoluble fraction contained kaolinite, CaCO3, aliphatic carbons, aromatic rings, carboxyl and hydroxyl groups reflected by the infrared spectra. Heavy metals were detected from the total mass.(2) Proteins dispersed PM2.5 in SLF, resulted in smaller hydrodynamic diameter (dH) and slower sedimentation rate. Conversely, phospholipids increased dH value and accelerated sedimentation rate. Bovine Serum Albumin (BSA) proteins promoted the PM2.5 dispersion in lung fluid and its transport to the remote body part, however phospholipids accelerated the PM2.5 aggregation and the large aggregates may deposit in alveoli.(3) Giant unilamellar vesicles (GUVs) and supported lipid bilayers (SLBs) were used as model cell membranes. PM2.5 adhered on and disrupted the membrane containing positively-charged lipids but not the membrane containing negatively-charged lipids, which was monitored by microscopy and a quartz crystal microbalance with dissipation (QCM-D). The cationic sites on membrane were necessary for PM2.5 adhesion, but membrane should be disrupted by the combined action of electrostatic forces and hydrogen bonds between PM2.5 oxygen containing groups and the lipid phosphate groups.(4) PM2.5 deteriorated the growth state of cells, inhibited cell viability, and stimulated the production of reactive oxygen species (ROS), and the effects are related to the dose of PM2.5. The effects of the whole PM2.5 are higher than its insoluble fractions and soluble fraction.Our results specified the roles of proteins and phospholipids in PM2.5 dispersion and transport, highly suggested that the health hazard of PM2.5 was related to the biomolecules in the lung fluid and the particle surface groups. Both the insoluble and soluble fraction of PM2.5 showed cytotoxicity, the insoluble fraction showed greater cytotoxicity due to the cell viability investigation.