Poor air quality is globally the largest environmental health risk. Epidemiological studies have uncovered clear relationships of gaseous pollutants and particulate matter (PM) with adverse health outcomes, including mortality by cardiovascular and respiratory diseases. Studies of health impacts by aerosols are highly multidisciplinary with a broad range of scales in space and time. We assess recent advances and future challenges regarding aerosol effects on health from molecular to global scales through epidemiological studies, field measurements, health-related properties of PM, and multiphase interactions of oxidants and PM upon respiratory deposition. Global modeling combined with epidemiological exposure-response functions indicates that ambient air pollution causes more than four million premature deaths per year. Epidemiological studies usually refer to PM mass concentrations, but some health effects may relate to specific constituents such as bioaerosols, polycyclic aromatic compounds, and transition metals. Various analytical techniques and cellular and molecular assays are applied to assess the redox activity of PM and the formation of reactive oxygen species. Multiphase chemical interactions of lung antioxidants with atmospheric pollutants are crucial to the mechanistic and molecular understanding of oxidative stress upon respiratory deposition. The role of distinct PM components in health impacts and mortality needs to be clarified by integrated research on various spatiotemporal scales for better evaluation and mitigation of aerosol effects on public health in the Anthropocene.

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Translocation of inhaled ultrafine particles from the lungs into the blood may impair cardiovascular function. We administered ultrafine (20-nm) and fine (200-nm) gold colloid or fluorescein-labeled polystyrene particles to mice intratracheally and examined their localization in the lung and extrapulmonary organs. Fifteen minutes after instillation, dispersed and agglomerated 20-nm gold colloid particles were observed on the surface of endothelial cells, on the alveolar surface, in endocytotic vesicles of alveolar epithelial cells, and in the basement membrane of the lung. A small but noteworthy amount of gold was detected in the liver, kidney, spleen, and heart by inductively coupled plasma-mass spectrometry. After administration of 20- or 200-nm fluorescent particles, free particles were detected infrequently in blood vessels, on the endocardial surface, and in the kidney and liver only in the mice that received 20-nm particles, whereas phagocytes containing 20- or 200-nm particles were found in the extrapulmonary tissues. Fluorescent particle-laden alveolar macrophages administered intratracheally translocated from alveoli to extrapulmonary organs via the blood circulation. Thus, small amounts of ultrafine particles are transported across the alveolar wall into the blood circulation via endocytotic pathways, but particle-laden alveolar macrophages translocate both ultrafine and fine particles from the lungs to the extrapulmonary organs.

Recent toxicological studies indicate that nanoparticles or ultrafine particles (< 100 nm) are more toxic than fine particles (< 2 microm) because of their greater surface area. It is well known that alveolar macrophages play an important role in the first defense against various environmental particles and microorganisms. This is accomplished by binding to a macrophage receptor with collagenous structure (MARCO), one of several scavenger-type receptors expressed on the cell surface of macrophages. MARCO has been shown to mediate the ingestion of unopsonized environmental particles such as TiO(2) and Fe(2)O(3) (1.3 microm in diameter). However, very little is known about the cellular uptake of nanoparticles. In the present study, we investigated whether MARCO mediates the uptake of nanoparticles by using fluorescent-tagged polystyrene particles (20 nm, 200 nm, and 1 microm in diameter). COS-7 cells were transfected with either MARCO cDNA or an empty vector, and the association of the particles with the cells were observed by fluorescence microscopy and atomic force microscopy. MARCO-transfected cells associated with all three sizes of particles in a time-dependent manner, while no obvious binding of particles occurred after 5 h to the empty vector-transfected cells. The uptake of particles by MARCO-transfected cells was partially inhibited by polyG. These results suggest that macrophages associate with nanoparticles (20 nm) at least in part through MARCO and that MARCO plays a role in clearing nanoparticles which can deposit in the alveolar region.