羊胎儿胸腺内脂多糖暴露改变细胞群体和结构。
Intraamniotic lipopolysaccharide exposure changes cell populations and structure of the ovine fetal thymus.
机构信息
Department of Pediatrics, School for Oncology and Developmental Biology, School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands.
出版信息
Reprod Sci. 2013 Aug;20(8):946-56. doi: 10.1177/1933719112472742. Epub 2013 Jan 11.
RATIONALE
Chorioamnionitis induces preterm delivery and acute involution of the fetal thymus which is associated with postnatal inflammatory disorders. We studied the immune response, cell composition, and architecture of the fetal thymus following intraamniotic lipopolysaccharide (LPS) exposure.
METHODS
Time-mated ewes received an intraamniotic injection of LPS 5, 12, or 24 hours or 2, 4, 8, or 15 days before delivery at 125 days gestational age (term = 150 days).
RESULTS
The LPS exposure resulted in decreased blood lymphocytes within 5 hours and decreased thymic corticomedullary ratio within 24 hours. Thymic interleukin 6 (IL6) and IL17 messenger RNA (mRNA) increased 5-fold 24 hours post-LPS exposure. Increased toll-like receptor 4 (TLR4) mRNA and nuclear factor κB positive cells at 24 hours after LPS delivery demonstrated acute thymic activation. Both TLR4 and IL1 mRNA increased by 5-fold and the number of Foxp3-positive cells (Foxp3+ cells) decreased 15 days after exposure.
CONCLUSION
Intraamniotic LPS exposure caused a proinflammatory response, involution, and a persistent depletion of thymic Foxp3+ cells indicating disturbance of the fetal immune homeostasis.
背景
绒毛膜羊膜炎会引发早产和胎儿胸腺的急性退化，这与产后炎症性疾病有关。我们研究了羊膜内注射脂多糖（LPS）后胎儿胸腺的免疫反应、细胞组成和结构。
方法
在妊娠 125 天时，将时间匹配的母羊接受羊膜内注射 LPS，注射时间分别为 5、12 或 24 小时前，或 2、4、8 或 15 天前。
结果
LPS 暴露会导致血液淋巴细胞在 5 小时内减少，胸腺皮质-髓质比例在 24 小时内减少。LPS 暴露后 24 小时，胸腺白细胞介素 6（IL6）和白细胞介素 17（IL17）信使 RNA（mRNA）增加 5 倍。LPS 给药后 24 小时，Toll 样受体 4（TLR4）mRNA 和核因子 κB 阳性细胞增加，表明急性胸腺激活。TLR4 和 IL1 mRNA 增加 5 倍，暴露后 15 天 Foxp3 阳性细胞（Foxp3+细胞）的数量减少。
结论
羊膜内 LPS 暴露引起促炎反应、退化和胎儿胸腺 Foxp3+细胞的持续耗竭，表明胎儿免疫稳态受到干扰。
Zotero 插件