Maneenil Gunlawadee, Kemp Matthew W, Kannan Paranthaman Senthamarai, Kramer Boris W, Saito Masatoshi, Newnham John P, Jobe Alan H, Kallapur Suhas G
Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, University of Cincinnati School of Medicine, Cincinnati, Ohio, United States of America; Department of Pediatrics, Faculty of Medicine, Prince of Songkla University, Thailand.
School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
PLoS One. 2015 Mar 20;10(3):e0119281. doi: 10.1371/journal.pone.0119281. eCollection 2015.
A fetal inflammatory response (FIR) in sheep can be induced by intraamniotic or selective exposure of the fetal lung or gut to lipopolysaccharide (LPS). The oral, nasal, and pharyngeal cavities (ONP) contain lymphoid tissue and epithelium that are in contact with the amniotic fluid. The ability of the ONP epithelium and lymphoid tissue to initiate a FIR is unknown.
To determine if FIR occurs after selective ONP exposure to LPS in fetal sheep.
Using fetal recovery surgery, we isolated ONP from the fetal lung, GI tract, and amniotic fluid by tracheal and esophageal ligation and with an occlusive glove fitted over the snout. LPS (5 mg) or saline was infused with 24 h Alzet pumps secured in the oral cavity (n = 7-8/group). Animals were delivered 1 or 6 days after initiation of the LPS or saline infusions.
The ONP exposure to LPS had time-dependent systemic inflammatory effects with changes in WBC in cord blood, an increase in posterior mediastinal lymph node weight at 6 days, and pro-inflammatory mRNA responses in the fetal plasma, lung, and liver. Compared to controls, the expression of surfactant protein A mRNA increased 1 and 6 days after ONP exposure to LPS.
ONP exposure to LPS alone can induce a mild FIR with time-dependent inflammatory responses in remote fetal tissues not directly exposed to LPS.
羊的胎儿炎症反应（FIR）可通过羊膜腔内注射或胎儿肺或肠道选择性暴露于脂多糖（LPS）诱导产生。口腔、鼻腔和咽腔（ONP）含有与羊水接触的淋巴组织和上皮细胞。ONP上皮细胞和淋巴组织引发FIR的能力尚不清楚。
确定在胎儿羊中选择性ONP暴露于LPS后是否会发生FIR。
采用胎儿复苏手术，通过气管和食管结扎以及在口鼻部佩戴封闭手套，将ONP与胎儿肺、胃肠道和羊水分离。将LPS（5mg）或生理盐水通过固定在口腔内的24小时Alzet泵注入（每组n = 7 - 8只）。在开始注入LPS或生理盐水后1天或6天分娩动物。
ONP暴露于LPS具有时间依赖性的全身炎症效应，表现为脐血白细胞变化、6天时后纵隔淋巴结重量增加以及胎儿血浆、肺和肝脏中的促炎mRNA反应。与对照组相比，ONP暴露于LPS后1天和6天，表面活性蛋白A mRNA的表达增加。
单独将ONP暴露于LPS可在未直接暴露于LPS的远端胎儿组织中诱导轻度FIR，并伴有时间依赖性炎症反应。
