World Trade Center Dust induces airway inflammation while promoting aortic endothelial dysfunction

Hernández, Michelle; Harrington, A. D.; Ma, Ying; Galdanes, Karen; Halzack, Beth; Zhong, Mianhua; Vaughan, Joshua M.; Sebasco, Ethan; Gordon, Terry; Lippmann, Morton; Chen, Lung Chi

doi:10.1016/j.taap.2020.115041

Cited by 9 publications

(6 citation statements)

References 36 publications

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“…Excitingly we found that among the 21 upregulated genes in peripheral blood, there were several involved [43]. This is consistent with the evidence that WTCPM exposure in rodents promotes an increase in polymorphonuclear neutrophils in nasal and bronchoalveolar lavage fluid [23] in agreement with the trend increase we found in the periphery in our study. This evidence is consistent with a peripherally mounted innate immune response to WTCPM dust exposure, which we hypothesize will synergistically propagate neuroinflammation to the brain.…”

supporting

confidence: 93%

“…No significant detection of the chemical elements was found in WT groups. We want to point out, that the levels of metal detectability are complex due to the variable efflux rates from the brain of many of and bronchoalveolar lavage fluid [23]. Binding Protein ␤ (Cebpβ).…”

Section: Most Of the Chemical Elements Investigated In Con-mentioning

confidence: 99%

“…Chromium is the most soluble heavy metal, and its high solubility might be one reason we specifically detected it our WTCPM animal model.Direct toxicity from WTCPM dust has been demonstrated in vivo, mainly in the respiratory and circulatory systems[11, 13]. In vitro, THP-1 macrophages exposed to WTC dust elicited the production of reactive nitrogen species and correlated directly with cytotoxicity[23]. The same study revealed significant polymorphonuclear neutrophil infiltrate into the bronchoalveolar lavage fluid and an increase of pro-inflammatory cytokines using mice treated with WTC dust.…”

mentioning

confidence: 90%

“…All mice 176 were exposed to repeated intranasal (IN) instillation of WTCPM 10-53 m. For this, 125 g/dose was 178 selected to achieve exposure burdens calculated to 179 reflect those faced by FR exposed to Ground Zero 180 air levels. The selected dosing amount of 125 l, 181 frequency, and sacrifice time point, were derived 182 from Hernández et al[23,24]. According to those studies, this dose was the most physiologically relevant for our studies, and a higher dose of WTCPM 10-53 m in C57BL/6J mice led to a ceiling effect (possibly due to airway blockage) and increased lethality with repeated dosing in a short period of time.The same authors described the human equivalent dosing calculations that were acquired usingallometric body weight factors of 0.67 (BW0.67) and 0.75 (BW0.75), considering the weight ratios of 0.02-0.03 kg for mice and 50-70 kg for humans and taking into account the FR intermediate exposure to WTCPM 10-53 m for an 8-h shift at Ground Zero which is on the order of ≈50 mg/kg.…”

mentioning

confidence: 99%

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Exposure to World Trade Center Dust Exacerbates Cognitive Impairment and Evokes a Central and Peripheral Pro-Inflammatory Transcriptional Profile in an Animal Model of Alzheimer’s Disease

Iban-Arias

Trageser

Yang

et al. 2023

JAD

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Background: The terrorist attacks on September 11, 2001, on the World Trade Center (WTC) led to intense fires and a massive dense cloud of toxic gases and suspended pulverized debris. In the subsequent years, following the attack and cleanup efforts, a cluster of chronic health conditions emerged among First Responders (FR) who were at Ground Zero for prolonged periods and were repeatedly exposed to high levels of WTC particulate matter (WTCPM). Among those are neurological complications which may increase the risk for the development of Alzheimer’s disease (AD) later in life. Objective: We hypothesize that WTCPM dust exposure affects the immune cross-talking between the periphery and central nervous systems that may induce brain permeability ultimately promoting AD-type phenotype. Methods: 5XFAD and wild-type mice were intranasally administered with WTCPM dust collected at Ground Zero within 72 h after the attacks. Y-maze assay and novel object recognition behavioral tests were performed for working memory deficits and learning and recognition memory, respectively. Transcriptomic analysis in the blood and hippocampus was performed and confirmed by RT qPCR. Results: Mice exposed to WTCPM dust exhibited a significant impairment in spatial and recognition short and long-term memory. Furthermore, the transcriptomic analysis in the hippocampal formation and blood revealed significant changes in genes related to immune-inflammatory responses, and blood-brain barrier disruption. Conclusion: These studies suggest a putative peripheral-brain immune inflammatory cross-talking that may potentiate cognitive decline, identifying for the first time key steps which may be therapeutically targetable in future studies in WTC FR.

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supporting

confidence: 93%

Section: Most Of the Chemical Elements Investigated In Con-mentioning

confidence: 99%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Exposure to World Trade Center Dust Exacerbates Cognitive Impairment and Evokes a Central and Peripheral Pro-Inflammatory Transcriptional Profile in an Animal Model of Alzheimer’s Disease

Iban-Arias

Trageser

Yang

et al. 2023

JAD

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“…In fact, large quantities of asbestos and asbestos–cement are used in the construction of buildings in Balkan and Asian countries. Previous evidence has shown that exposure to dust produced by collapsing buildings has inflammatory and cytotoxic effects on the pulmonary endothelium, 13 and long-term exposure to asbestos fibres is the main aetiological cause of MM. 14 A possible role of asbestos exposure has been hypothesised in a case of MEC.…”

Section: Global Health Problem Analysismentioning

confidence: 99%

War journalism: an occupational exposure

et al. 2021

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Apart from the risk of accidents, war theatres present a hazard related to numerous long-lasting toxic agents. For 10 years, a >60-year-old male journalist worked in war theatres in the Far and Near East where he was exposed to asbestos and other toxic substances (metals, silica, clays, polycyclic aromatic hydrocarbons and other organic substances) contained in dust and smoke of destroyed buildings. More than 15 years later, he developed a mucoepidermoid carcinoma of the soft palate and, subsequently, a pleural malignant mesothelioma. The safety of war journalists should focus not only on preventing the risk of being killed, but also on providing protection from toxic and carcinogenic agents. Exposure to substances released during the destruction of buildings can also pose a carcinogenic risk for survivors.

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Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

Pandics,

Major,

Fazekas-Pongor

et al. 2023

GeroScience

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The aging population worldwide is facing a significant increase in age-related non-communicable diseases, including cardiovascular and brain pathologies. This comprehensive review paper delves into the impact of the exposome, which encompasses the totality of environmental exposures, on unhealthy aging. It explores how environmental factors contribute to the acceleration of aging processes, increase biological age, and facilitate the development and progression of a wide range of age-associated diseases. The impact of environmental factors on cognitive health and the development of chronic age-related diseases affecting the cardiovascular system and central nervous system is discussed, with a specific focus on Alzheimer’s disease, Parkinson’s disease, stroke, small vessel disease, and vascular cognitive impairment (VCI). Aging is a major risk factor for these diseases. Their pathogenesis involves cellular and molecular mechanisms of aging such as increased oxidative stress, impaired mitochondrial function, DNA damage, and inflammation and is influenced by environmental factors. Environmental toxicants, including ambient particulate matter, pesticides, heavy metals, and organic solvents, have been identified as significant contributors to cardiovascular and brain aging disorders. These toxicants can inflict both macro- and microvascular damage and many of them can also cross the blood–brain barrier, inducing neurotoxic effects, neuroinflammation, and neuronal dysfunction. In conclusion, environmental factors play a critical role in modulating cardiovascular and brain aging. A deeper understanding of how environmental toxicants exacerbate aging processes and contribute to the pathogenesis of neurodegenerative diseases, VCI, and dementia is crucial for the development of preventive strategies and interventions to promote cardiovascular, cerebrovascular, and brain health. By mitigating exposure to harmful environmental factors and promoting healthy aging, we can strive to reduce the burden of age-related cardiovascular and brain pathologies in the aging population.

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World Trade Center Dust induces airway inflammation while promoting aortic endothelial dysfunction

Cited by 9 publications

References 36 publications

Exposure to World Trade Center Dust Exacerbates Cognitive Impairment and Evokes a Central and Peripheral Pro-Inflammatory Transcriptional Profile in an Animal Model of Alzheimer’s Disease

Exposure to World Trade Center Dust Exacerbates Cognitive Impairment and Evokes a Central and Peripheral Pro-Inflammatory Transcriptional Profile in an Animal Model of Alzheimer’s Disease

War journalism: an occupational exposure

Exposome and unhealthy aging: environmental drivers from air pollution to occupational exposures

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