Chlorinated Polycyclic Aromatic Hydrocarbons Induce Immunosuppression in THP-1 Macrophages Characterized by Disrupted Amino Acid Metabolism

Li, Xinyan; Ma, Ming; Zhao, Bilin; Li, Na; Fang, Ling; Wang, Donghong; Luan, Tiangang

doi:10.1021/acs.est.2c06471

Cited by 14 publications

(13 citation statements)

References 46 publications

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“…This study is supported by others showing that PM exposure from air pollution causes systemic inflammation [16] and the release of cytokines IL-6 and IL-8 in human bronchial epithelial cells and alveolar macrophages [17]. In addition, PAH exposures also hyperstimulate maternal immune cells in mouse models and exert a cytotoxic effect on human-derived macrophages [18,19].…”

Section: Inflammation From Wildfire Smoke Exposuresupporting

confidence: 82%

“…These findings provide the first evidence that wildfire smoke exposure in pregnancy may dysregulate placental immune status, particularly with exposures earlier in pregnancy. These results are concerning and build on previous examples that have shown chemical components of wildfire smoke such as polycyclic aromatic hydrocarbons (PAHs) to act as contribute to an immunosuppressive effect on macrophages [19]. There is little data on the composition of wildfires from distinct wildfire events.…”

Section: Discussionmentioning

confidence: 56%

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Gestational age-dependent decrease in fetal Hofbauer cells in placentas from pregnancies exposed to wildfire smoke in California

Basilio

Ozarslan

Buarpung

et al. 2023

Preprint

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OBJECTIVE: Wildfires are more common over the last decade and the frequency of wildfire events has been accelerated by climate change. The existing body of literature suggests that exposure to wildfire smoke during pregnancy contributes to adverse perinatal outcomes such as preterm birth and fetal growth restriction. We hypothesize that exposures to wildfire smoke and its constituents triggers a fetal inflammatory response which contributes to pathological changes that underlie these adverse pregnancy outcomes. In this study, we quantified the presence of fetal macrophages (i.e., Hofbauer cells) in human placentas obtained between 2018 and 2020 to assess the relationship between fetal immune status and wildfire exposure. STUDY DESIGN: We collected placentas from pregnancies from two hospitals in San Francisco over a two-year period that included two severe major wildfires. The average particulate matter < 2.5 μm (PM2.5) or wildfire specific PM2.5 levels were estimated over the gestational duration of each sample. Immunostaining against CK7 and CD68 was performed to identify intravillous fetal Hofbauer cells. We assessed the gestational-age dependent relationship between placental CD68+ cell density and mean daily PM2.5 or wildfire specific PM2.5 via linear regression and Welch's t-test. Additionally, we compared placental CD68+ cell density with estimated peak wildfire exposures during the gestation to determine if timing of exposure during pregnancy may influence the occurrence of Hofbauer cells in the placenta. RESULTS: The gestational ages ranged from 7-41 weeks (n = 67). The majority of samples were collected during one of two major wildfire events in Northern California (70%; n = 47). In general, we observed a significant inverse relationship between placental CD68 density and PM2.5 or wildfire specific PM2.5, however, these associations were only observed in first or second trimester samples, and not in term samples. For example, among first trimester samples (n=22), we observed lower mean CD68 density among samples likely to be exposed to wildfire events (mean = 1.42, SD = 0.8) as compared to those not exposed (mean = 3.73, SD = 1.983) (p = 0.0015). Based on our linear regression model results, we predicted that a one μg/m3 increase in daily mean wildfire PM2.5 was associated with a 0.457 decrease in CD68 density (β =-0.457; 95% CI: -0.722, -0.193). This association was also significant for daily mean overall PM2.5, though smaller in magnitude (β = -0.139; 95% CI: -0.218, -0.059). CONCLUSIONS: Our results suggest that wildfire smoke exposures are associated with decreased presence of fetal Hofbauer cells in first and second trimester placentas, suggesting exposure may lead to impaired placental function via altered presence of fetal Hofbauer cells and changes in immune status.

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Section: Inflammation From Wildfire Smoke Exposuresupporting

confidence: 82%

Section: Discussionmentioning

confidence: 56%

Gestational age-dependent decrease in fetal Hofbauer cells in placentas from pregnancies exposed to wildfire smoke in California

Basilio

Ozarslan

Buarpung

et al. 2023

Preprint

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“…172 For XPAHs, prior research has revealed that specific XPAHs (9-chloroanthracene and 2,7-dichlorofluorene) could instigate immune dysfunction and metabolic disruption in THP-1 macrophages, with clear evidence of immunosuppression and complex modifications in the multicytokine/chemokine network. 173 As for OPAHs, studies on cellular effects of OPAHs in PM 2.5 report diminished cell viability, increased nitric oxide, and escalated production of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6). 174 16 Furthermore, benzanthrone has been found to exert immunomodulatory effects in mice via oxidative stress and inflammatory mediators.…”

Section: Derivatives and Potential Exposure Biomarkersmentioning

confidence: 99%

A Systematic Review of Polycyclic Aromatic Hydrocarbon Derivatives: Occurrences, Levels, Biotransformation, Exposure Biomarkers, and Toxicity

Peng,

Dong,

et al. 2023

Environ. Sci. Technol.

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Polycyclic aromatic hydrocarbon (PAH) derivatives constitute a significant class of emerging contaminants that have been ubiquitously detected in diverse environmental matrixes, with some even exhibiting higher toxicities than their corresponding parent PAHs. To date, compared with parent PAHs, fewer systematic summaries and reanalyses are available for PAH derivatives with great environmental concerns. This review summarizes the current knowledge on the chemical species, levels, biotransformation patterns, chemical analytical methods, internal exposure routes with representative biomarkers, and toxicity of PAH derivatives, primarily focusing on nitrated PAHs (NPAHs), oxygenated PAHs (OPAHs), halogenated PAHs (XPAHs), and alkylated PAHs (APAHs). A collection of 188 compounds from four categories, 44 NPAHs, 36 OPAHs, 56 APAHs, and 52 XPAHs, has been compiled from 114 studies that documented the environmental presence of PAH derivatives. These compounds exhibited weighted average air concentrations that varied from a lower limit of 0.019 pg/m3 to a higher threshold of 4060 pg/m3. Different analytical methods utilizing comprehensive two-dimensional gas chromatography coupled with high-resolution time-of-flight mass spectrometry (GC × GC-TOF-MS), gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS), comprehensive two-dimensional gas chromatography coupled to quadrupole mass spectrometry (GC × GC-QQQ-MS), and Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS), that adopted untargeted strategies for the identification of PAH derivatives are also reviewed here. Additionally, an in-depth analysis of biotransformation patterns for each category is provided, including the likelihood of specific biotransformation reaction types. For the toxicity, we primarily summarized key metabolic activation pathways, which could result in the formation of reactive metabolites capable of covalently bonding with DNA and tissue proteins, and potential health outcomes such as carcinogenicity and genotoxicity, oxidative stress, inflammation and immunotoxicity, and developmental toxicity that might be mediated by the aryl hydrocarbon receptor (AhR). Finally, we pinpoint research challenges and emphasize the need for further studies on identifying PAH derivatives, tracking external exposure levels, evaluating internal exposure levels and associated toxicity, clarifying exposure routes, and considering mixture exposure effects. This review aims to provide a broad understanding of PAH derivatives’ identification, environmental occurrence, human exposure, biotransformation, and toxicity, offering a valuable reference for guiding future research in this underexplored area.

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“…Mainly originating from incomplete combustion and chemical synthesis, they are frequently detected in various environmental and food sources, including seafood, rice, air, soils, and surface water . Research has revealed higher levels of Cl-Ants in indoor cockroaches compared to indoor dust, signifying a substantial bioaccumulation. , Moreover, recent findings have confirmed the presence of Cl-Ants in human serum, with higher levels observed in occupational exposures compared to environmental exposures. , However, research into the toxicity of Cl-Ants was limited, with individual studies indicating potential health risks such as DNA damage in rat hepatoma cells and immunosuppression in macrophages . The current majority of research on PAHs/Cl-PAHs is predominantly focused on the AhR pathway.…”

Section: Introductionmentioning

confidence: 99%

Chlorinated Anthracenes Induced Pulmonary Immunotoxicity in 3D Coculture Spheroids Simulating the Lung Microenvironment

Li,

Zhou,

Luo

et al. 2024

Environ. Sci. Technol.

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Chlorinated Polycyclic Aromatic Hydrocarbons Induce Immunosuppression in THP-1 Macrophages Characterized by Disrupted Amino Acid Metabolism

Cited by 14 publications

References 46 publications

Gestational age-dependent decrease in fetal Hofbauer cells in placentas from pregnancies exposed to wildfire smoke in California

Gestational age-dependent decrease in fetal Hofbauer cells in placentas from pregnancies exposed to wildfire smoke in California

A Systematic Review of Polycyclic Aromatic Hydrocarbon Derivatives: Occurrences, Levels, Biotransformation, Exposure Biomarkers, and Toxicity

Chlorinated Anthracenes Induced Pulmonary Immunotoxicity in 3D Coculture Spheroids Simulating the Lung Microenvironment

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