Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative ...to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes.
As a critical air pollutant, PM2.5 is proved to be associated with numerous adverse health impacts and pose serious challenges to human life. This situation is especially important for China as the ...most populous and one of the heaviest PM2.5 polluted country in the world. However, health burden estimations reported for China in previous studies may be biased due to the usage of PM2.5 concentrations at a coarsely spatial resolution, as well as the ignorance of the spatial discrepancies of parameters (e.g. respiratory rate) employed in the exposure-response function. This study therefore utilized a hybrid remote sensing-geostatistical approach to refine PM2.5 concentrations at 1 km resolution across mainland China from 2013 to 2017. Meanwhile, nationwide exposure parameters were for the first time introduced to weight the integrated exposure response (IER) function to calculate and spatially reallocate the corresponding PM2.5-attributable premature deaths at 1 km resolution. Results showed that annually averaged PM2.5 concentrations in mainland China decreased by 39.5%, from 59.1 μg/m3 in 2013 to 35.8 μg/m3 in 2017. Subsequently, PM2.5 attributable premature deaths reduced 12.6%, from 1.20 million (95% CI: 0.57; 1.71) in 2013 to 1.05 million (95% CI: 0.44; 1.44) in 2017. This declining trend was found in most parts of China except some areas in Xinjiang, Jilin, and Heilongjiang provinces. As a result, 214,821 (95% CI: 96,675; 302,897) life were saved with an estimated monetary value of US$ 210.14 billion (2011 values). However, it has to be acknowledged that, the central and northern China within priority areas of air pollution control were still experiencing high numbers of premature deaths due to the severe PM2.5 pollution and high-density population. But more worrying than these priority areas are those Harbin-Changchun Metropolitan Region, City Belt in Central Henan and Yangtze-Huaihe City Belt in non-priority areas, which also have been seriously suffering PM2.5 attributable premature deaths over 28, 000 cases per year. In conclusion, despite the huge gain in life-saving effects in China over the past five years with the help of air pollution intervention policy, future work on cleaner air and better human health is still strongly needed, especially in non-priority areas of air pollution control.
•PM2.5 related premature deaths across China at 1 km resolution were estimated.•Spatially refined premature deaths were reallocated with exposure enhanced IER model.•Clean air action over the past five years received significant health benefits.•Strategy for air pollution intervention is necessary in non-priority areas of China.
•A neuroimmunologic link between stress, inflammation, air pollution, was identified.•A model of social-environmental adversity and lifespan health was proposed.•We posit that early life stress and ...air pollution jointly drive health disparity.
Socially disadvantaged individuals are at greater risk for simultaneously being exposed to adverse social and environmental conditions. Although the mechanisms underlying joint effects remain unclear, one hypothesis is that toxic social and environmental exposures have synergistic effects on inflammatory processes that underlie the development of chronic diseases, including cardiovascular disease, diabetes, depression, and certain types of cancer. In the present review, we examine how exposure to two risk factors that commonly occur with social disadvantage—early life stress and air pollution—affect health. Specifically, we identify neuroimmunologic pathways that could link early life stress, inflammation, air pollution, and poor health, and use this information to propose an integrated, multi-level model that describes how these factors may interact and cause health disparity across individuals based on social disadvantage. This model highlights the importance of interdisciplinary research considering multiple exposures across domains and the potential for synergistic, cross-domain effects on health, and may help identify factors that could potentially be targeted to reduce disease risk and improve lifespan health.
Micro- and nanoplastic particles (MNP) are omnipresent as either pollution or intentionally used in consumer products, released from packaging or even food. There is an exponential increase in the ...production of plastics. With the realization of bioaccumulation in humans, toxicity research is quickly expanding. There is a rapid increase in the number of papers published on the potential implications of exposure to MNP which necessitates a call for quality criteria to be applied when doing the research. At present, most papers on MNP describe the effects of commercially available polymer (mostly polystyrene) beads that are typically not the MNP of greatest concern. This is not a fault of the research community, necessarily, as the MNPs to which humans are exposed are usually not available in the quantities needed for toxicological research and innovations are needed to supply environmentally-relevant MNP models. In addition, like we have learned from decades of research with particulate matter and engineered nanomaterials, sample physicochemical characteristics and preparation can have major impacts on the biological responses and interpretation of the research findings. Lastly, MNP dosimetry may pose challenges as (1) we are seeing early evidence that plastics are already in the human body at quite high levels that may be difficult to achieve in acute in vitro studies and (2) plastics are already in the diets fed to preclinical models. This commentary highlights the pitfalls and recommendations for particle and fibre toxicologists that should be considered when performing and disseminating the research.
•Air pollution and associated exposure risks are decreasing in China since 2013.•Personal air pollution exposure behaviors show significant spatial discrepancies.•China’s air pollution exposure risk ...can be prevented by both the state and individuals’ efforts.•Localized measures for reducing air pollution exposure risk across China are needed.•Personal behavior changes play a growing role in reducing air pollution exposure risk.
China has made great efforts towards air pollutant concentration control during the past five years, which has led to positive outcomes. However, air pollutant concentration focused efforts were considered separately from human exposure risk. And this might result in a misunderstanding that reducing exposure risk can only rely on the national level measures of air pollutant control. This study integrates the first Chinese survey of human activity patterns and the spatially continuous high-resolution PM2.5 concentration maps to reveal the spatial and temporal variations of China’s air pollution exposure risk from 2013 to 2017. More importantly, the effects on risk reduction from multi-scale and multi-object perspectives (reductions of ambient PM2.5 concentrations by national or provincial measures and changes of individual behavior patterns by personal efforts) are deeply investigated. Results show that the reductions of PM2.5 concentration and associated reductions of exposure risk from 2013 to 2017 were 40% and 35.7%, respectively. They also showed that both the reduction of PM2.5 concentrations and change of personal behavior patterns were effective for risk reduction when China’s total PM2.5 exposure risk was higher than 1.58. However, only individual behavior changes contributed to risk reduction for scenarios with state-level risk value below 1.58. For regional strategies, threshold values for PM2.5 exposure risk control differentiating national measures or personal efforts were spatially and temporally dependent. The role of personal behavior changes on PM2.5 exposure risk reduction was growing in these five years with concentration rapidly decreasing regions. The findings suggest that people-centered air pollution exposure risk prevention not only depends on government management for air pollution control, but also on individual changes of activity patterns. Efforts from the state and individuals are both essential for reducing air pollution exposure risk in China, especially growing individual efforts are needed in regions with the decreasing air pollutant concentrations in the coming future. Moreover, this study mainly discussed the PM2.5 exposure risk from the macroscopic perspective, the research at the microcosmic perspective is also needed in the further study.
Anti-inflammatory and proinflammatory responses in macrophages are influenced by cellular metabolism. Macrophages are the primary phagocyte in mucosal environments (i.e., intestinal tract and lungs) ...acting as first-line defense against microorganisms and environmental pollutants. Given the extensive contamination of our food and water sources with microplastics, we aimed to examine the metabolic response in macrophages to microplastic particles (MPs). Utilizing murine macrophages, we assessed the metabolic response of macrophages after polystyrene MP phagocytosis. The phagocytosis of MP by macrophages induced a metabolic shift toward glycolysis and a reduction in mitochondrial respiration that was associated with an increase of cell surface markers CD80 and CD86 and cytokine gene expression associated with glycolysis. The gastrointestinal consequences of this metabolic switch in the context of an immune response remain uncertain, but the global rise of plastic pollution and MP ingestion potentially poses an unappreciated health risk.
Graphical abstract
Macrophage phagocytosis of microplastics alters cellular metabolism.
- Macrophages cannot degrade PS MP.
- MP phagocytosis increases glycolysis in murine macrophages.
- MP phagocytosis reduces mitochondrial respiration in murine macrophages.
Pulmonary exposure to multiwalled carbon nanotubes (MWCNTs) causes indirect systemic inflammation through unknown pathways. MWCNTs translocate only minimally from the lungs into the systemic ...circulation, suggesting that extrapulmonary toxicity may be caused indirectly by lung-derived factors entering the circulation. To assess a role for MWCNT-induced circulating factors in driving neuroinflammatory outcomes, mice were acutely exposed to MWCNTs (10 or 40 μg/mouse) via oropharyngeal aspiration. At 4 h after MWCNT exposure, broad disruption of the blood-brain barrier (BBB) was observed across the capillary bed with the small molecule fluorescein, concomitant with reactive astrocytosis. However, pronounced BBB permeation was noted, with frank albumin leakage around larger vessels (>10 μm), overlain by a dose-dependent astroglial scar-like formation and recruitment of phagocytic microglia. As affirmed by elevated inflammatory marker transcription, MWCNT-induced BBB disruption and neuroinflammation were abrogated by pretreatment with the rho kinase inhibitor fasudil. Serum from MWCNT-exposed mice induced expression of adhesion molecules in primary murine cerebrovascular endothelial cells and, in a wound-healing in vitro assay, impaired cell motility and cytokinesis. Serum thrombospondin-1 level was significantly increased after MWCNT exposure, and mice lacking the endogenous receptor CD36 were protected from the neuroinflammatory and BBB permeability effects of MWCNTs. In conclusion, acute pulmonary exposure to MWCNTs causes neuroinflammatory responses that are dependent on the disruption of BBB integrity.
Abstract Background and aims Obstructive sleep apnea (OSA) is characterized by intermittent airway obstruction and systemic hypoxia during sleep, which can contribute to an increase in reactive ...oxygen species, vascular remodeling, vasoconstriction and ultimately cardiovascular disease. Continuous positive airway pressure (CPAP) is a clinical therapy that maintains airway patency and mitigates several symptoms of OSA. However, it is currently unknown whether CPAP therapy also reduces the overall inflammatory potential in the circulation; to address this in an unbiased manner, we applied a novel endothelial biosensor approach, the serum cumulative inflammatory potential (SCIP) assay. Methods We studied healthy controls (n = 7), OSA subjects receiving no treatment, (OSA controls) (n = 7) and OSA subjects receiving CPAP for 3 months (n = 8). Serum was obtained from OSA subjects before and after CPAP or no treatment. A battery of quantitative and functional assays was performed to assess the serum inflammatory potential, in terms of endothelial responses. For the SCIP assay, human coronary artery endothelial cells (hCAECs) were incubated with 5% serum in media from individual subjects for 4 h. qPCR was performed to assess endothelial inflammatory transcript (ICAM-1, VCAM-1, IL-8, P-selectin, CCL5, and CXCL12) responses to serum. Additionally, transendothelial resistance was measured in serum-incubated hCAECs following leukocyte challenge. Results hCAECs exhibited significant increases in VCAM-1, ICAM-1, IL-8 and P-selectin mRNA when incubated with serum from OSA patients compared to serum from healthy control subjects. Furthermore, compared to no treatment, serum from CPAP-treated individuals was less potent at inducing inflammatory gene expression in the SCIP assay. Similarly, in a leukocyte adhesion assay, naïve cells treated with serum from patients who received CPAP exhibited improved endothelial barrier function than cells treated with OSA control serum. Conclusions OSA results in greater serum inflammatory potential, thereby driving endothelial activation and dysfunction.
Abstract
The unique physicochemical properties of carbon nanomaterials and their ever-growing utilization generate a serious concern for occupational risk. Pulmonary exposure to these nanoparticles ...induces local and systemic inflammation, cardiovascular dysfunction, and even cognitive deficits. Although multiple routes of extrapulmonary toxicity have been proposed, the mechanism for and manner of neurologic effects remain minimally understood. Here, we examine the cerebral spinal fluid (CSF)-derived peptidomic fraction as a reflection of neuropathological alterations induced by pulmonary carbon nanomaterial exposure. Male C57BL/6 mice were exposed to 10 or 40 µg of multiwalled carbon nanotubes (MWCNT) by oropharyngeal aspiration. Serum and CSFs were collected 4 h post exposure. An enriched peptide fraction of both biofluids was analyzed using ion mobility-enabled data-independent mass spectrometry for label-free quantification. MWCNT exposure induced a prominent peptidomic response in the blood and CSF; however, correlation between fluids was limited. Instead, we determined that a MWCNT-induced peptidomic shift occurred specific to the CSF with 292 significant responses found that were not in serum. Identified MWCNT-responsive peptides depicted a mechanism involving aberrant fibrinolysis (fibrinopeptide A), blood-brain barrier permeation (homeobox protein A4), neuroinflammation (transmembrane protein 131L) with reactivity by astrocytes and microglia, and a pro-degradative (signal transducing adapter molecule, phosphoglycerate kinase), antiplastic (AF4/FMR2 family member 1, vacuolar protein sorting-associated protein 18) state with the excitation-inhibition balance shifted to a hyperexcited (microtubule-associated protein 1B) phenotype. Overall, the significant pathologic changes observed were consistent with early neurodegenerative disease and were diagnostically reflected in the CSF peptidome.
Among manufactured or engineered nanoparticles, carbon black (CB) has largest production worldwide and is also an occupational respiratory hazard commonly seen in rubber industry. Few studies have ...assessed the risk for cardiovascular disease in carbon black exposed populations. An endothelial biosensor assay was used to quantify the capacity of sera from 82 carbon black packers (CBP) and 106 non-CBPs to induce endothelial cell activation ex vivo. The mediation effect of circulatory proinflammatory factors on the association between carbon black exposure and endothelial cell activation was assessed and further validated using in vitro intervention experiments. The average elemental carbon level inside carbon black bagging facilities was 657.0 mug/m.sup.3, which was 164-fold higher than that seen in reference areas (4.0 mug/m.sup.3). A global index was extracted from mRNA expression of seven candidate biosensor genes using principal component analysis and used to quantify the magnitude of endothelial cell activation. This global index was found to be significantly altered in CBPs compared to non-CBPs (P < 0.0001), however this difference did not vary by smoking status (P = 0.74). Individual gene analyses identified that de novo expression of key adhesion molecules (e.g., ICAM and VCAM) and chemotactic factors (e.g., CCL2, CCL5, and CXCL8) responsible for the recruitment of leukocytes was dramatically induced in CBPs with CXCL8 showing the highest fold of induction (relative quantification = 9.1, P < 0.0001). The combination of mediation analyses and in vitro functional validation confirmed TNF-alpha, IL-1beta, and IL-6 as important circulatory factors mediating the effects of carbon black exposure on endothelial cell activation responses. Inflammatory mediators in sera from CBPs may bridge carbon black exposure and endothelial cell activation response assessed ex vivo. CBPs may have elevated risk for cardiovascular diseases when comorbidity exists. Our study may serve as a benchmark for understanding health effects of engineered carbon based nanoparticles with environmental and occupational health relevance.
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