Black Carolyn, Gerriets Joan E, Fontaine Justin H, Harper Richart W, Kenyon Nicholas J, Tablin Fern, Schelegle Edward S, Miller Lisa A
1 California National Primate Research Center.
2 Division of Pulmonary and Critical Care Medicine, School of Medicine, and.
Am J Respir Cell Mol Biol. 2017 May;56(5):657-666. doi: 10.1165/rcmb.2016-0380OC.
The long-term health effects of wildfire smoke exposure in pediatric populations are not known. The objectives of this study were to determine if early life exposure to wildfire smoke can affect parameters of immunity and airway physiology that are detectable with maturity. We studied a mixed-sex cohort of rhesus macaque monkeys that were exposed as infants to ambient wood smoke from a series of Northern California wildfires in the summer of 2008. Peripheral blood mononuclear cells (PBMCs) and pulmonary function measures were obtained when animals were approximately 3 years of age. PBMCs were cultured with either LPS or flagellin, followed by measurement of secreted IL-8 and IL-6 protein. PBMCs from a subset of female animals were also evaluated by Toll-like receptor (TLR) pathway mRNA analysis. Induction of IL-8 protein synthesis with either LPS or flagellin was significantly reduced in PBMC cultures from wildfire smoke-exposed female monkeys. In contrast, LPS- or flagellin-induced IL-6 protein synthesis was significantly reduced in PBMC cultures from wildfire smoke-exposed male monkeys. Baseline and TLR ligand-induced expression of the transcription factor, RelB, was globally modulated in PBMCs from wildfire smoke-exposed monkeys, with additional TLR pathway genes affected in a ligand-dependent manner. Wildfire smoke-exposed monkeys displayed significantly reduced inspiratory capacity, residual volume, vital capacity, functional residual capacity, and total lung capacity per unit of body weight relative to control animals. Our findings suggest that ambient wildfire smoke exposure during infancy results in sex-dependent attenuation of systemic TLR responses and reduced lung volume in adolescence.
儿童群体接触野火烟雾对健康的长期影响尚不清楚。本研究的目的是确定生命早期接触野火烟雾是否会影响成熟后可检测到的免疫参数和气道生理参数。我们研究了一组恒河猴，这些猴子在婴儿期接触了2008年夏季北加利福尼亚一系列野火产生的环境木烟。当动物约3岁时，获取外周血单核细胞（PBMC）和肺功能测量值。将PBMC与脂多糖（LPS）或鞭毛蛋白一起培养，然后测量分泌的白细胞介素-8（IL-8）和白细胞介素-6（IL-6）蛋白。还通过Toll样受体（TLR）途径mRNA分析评估了一部分雌性动物的PBMC。在接触野火烟雾的雌性猴子的PBMC培养物中，LPS或鞭毛蛋白诱导的IL-8蛋白合成显著降低。相比之下，在接触野火烟雾的雄性猴子的PBMC培养物中，LPS或鞭毛蛋白诱导的IL-6蛋白合成显著降低。接触野火烟雾的猴子的PBMC中，转录因子RelB的基线表达和TLR配体诱导的表达受到整体调节，其他TLR途径基因也以配体依赖的方式受到影响。与对照动物相比，接触野火烟雾的猴子每单位体重的吸气量、残气量、肺活量、功能残气量和肺总量显著降低。我们的研究结果表明，婴儿期接触环境野火烟雾会导致青春期全身TLR反应的性别依赖性减弱和肺容量降低。
