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DOI | 10.1289/EHP1878 |
Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice | |
Henderson, Michael W.1,3; Madenspacher, Jennifer H.1; Whitehead, Gregory S.1; Thomas, Seddon Y.1; Aloor, Jim J.1,4; Gowdy, Kymberly M.2; Fessler, Michael B.1 | |
2017-09-01 | |
发表期刊 | ENVIRONMENTAL HEALTH PERSPECTIVES |
ISSN | 0091-6765 |
EISSN | 1552-9924 |
出版年 | 2017 |
卷号 | 125期号:9 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | BACKGROUND: Arsenic exposure via drinking water impacts millions of people worldwide. Although arsenic has been associated epidemiologically with increased lung infections, the identity of the lung cell types targeted by peroral arsenic and the associated immune mechanisms remain poorly defined. OBJECTIVES: We aimed to determine the impact of peroral arsenic on pulmonary antibacterial host defense. METHODS: Female C57BL/6 mice were administered drinking water with 0, 250 ppb, or 25 ppm sodium arsenite for 5 wk and then challenged intratracheally with Klebsiella pneumoniae, Streptococcus pneumoniae, or lipopolysaccharide. Bacterial clearance and immune responses were profiled. RESULTS: Arsenic had no effect on bacterial clearance in the lung or on the intrapulmonary innate immune response to bacteria or lipopolysaccharide, as assessed by neutrophil recruitment to, and cytokine induction in, the airspace. Alveolar macrophage TNF alpha production was unaltered. By contrast, arsenic-exposed mice had significantly reduced plasma TNF alpha in response to systemic lipopolysaccharide challenge, together suggesting that the local airway innate immune response may be relatively preserved from arsenic intoxication. Despite intact intrapulmonary bacterial clearance during pneumonia, arsenic-exposed mice suffered dramatically increased bacterial dissemination to the bloodstream. Mechanistically, this was linked to increased respiratory epithelial permeability, as revealed by intratracheal FITC-dextran tracking, serum Club Cell protein 16 measurement, and other approaches. Consistent with harrier disruption at the alveolar level, arsenic-exposed mice had evidence for alveolar epithelial type 1 cell injury. CONCLUSIONS: Peroral arsenic has little effect on local airway immune responses to bacteria but compromises respiratory epithelial barrier integrity, increasing systemic translocation of inhaled pathogens and small molecules. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000461478500004 |
WOS类目 | Environmental Sciences ; Public, Environmental & Occupational Health ; Toxicology |
WOS研究方向 | Environmental Sciences & Ecology ; Public, Environmental & Occupational Health ; Toxicology |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/22464 |
专题 | 资源环境科学 |
作者单位 | 1.NIEHS, Immun Inflammat & Dis Lab, NIH, US DEPT HHS, POB 12233, Res Triangle Pk, NC 27709 USA; 2.East Carolina Univ, Dept Pharmacol & Toxicol, Brody Sch Med, Greenville, NC 27858 USA; 3.Univ N Carolina, UNC Sch Med, Dept Pathol & Lab Med, CB7035,Genet Med Bldg, Chapel Hill, NC 27599 USA; 4.East Carolina Univ, East Carolina Diabet & Obes Inst, Dept Physiol, ECHI 4101C, Greenville, NC 27834 USA |
推荐引用方式 GB/T 7714 | Henderson, Michael W.,Madenspacher, Jennifer H.,Whitehead, Gregory S.,et al. Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice[J]. ENVIRONMENTAL HEALTH PERSPECTIVES,2017,125(9). |
APA | Henderson, Michael W..,Madenspacher, Jennifer H..,Whitehead, Gregory S..,Thomas, Seddon Y..,Aloor, Jim J..,...&Fessler, Michael B..(2017).Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice.ENVIRONMENTAL HEALTH PERSPECTIVES,125(9). |
MLA | Henderson, Michael W.,et al."Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice".ENVIRONMENTAL HEALTH PERSPECTIVES 125.9(2017). |
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