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Inflammation-Induced Preterm Birth in a Murine Model is Associated with Increases in Fetal Macrophages and Circulating Erythroid Precursors

炎症 胎儿 脂多糖 医学 轻浮 小胶质细胞 胎盘 病理 促红细胞生成素 免疫学 中枢神经系统 内科学 生物 怀孕 遗传学
作者
Linda M. Ernst,Juan M. Gonzalez,Ella Ofori,Michal A. Elovitz
出处
期刊:Pediatric and Developmental Pathology [SAGE]
卷期号:13 (4): 273-281 被引量:14
标识
DOI:10.2350/09-05-0649-oa.1
摘要

The presence of intrauterine inflammation has been associated with adverse neurologic outcomes in preterm infants, but the precise mechanisms of fetal brain injury remain unclear. We sought to evaluate inflammatory cell trafficking, fetal organ damage, and molecular regulation in the fetoplacental unit using an established mouse model of preterm birth associated with intrauterine inflammation. Gestational sacs were harvested 6 hours after intrauterine infusion of saline or lipopolysaccharide (LPS). Histologic, immunohistochemical, and molecular investigations were performed to identify target organ damage and the cellular phenotype of inflammatory cells and to quantify circulating inflammatory and hematopoietic mediators within the placental and fetal tissue. There was widespread increase in fetal macrophages in LPS-exposed pups, including within the leptomeninges of the brain, associated with significantly higher of interleukin 6 levels in LPS-exposed pups. Although no specific central nervous system injury (necrosis or apoptosis) was documented, liver hematomas were seen significantly more frequently in LPS-exposed pups. Circulating nucleated fetal erythrocytes were also present more frequently with LPS exposure without significantly higher erythropoietin levels than saline-exposed mice. The presence of increased macrophages, increased circulating interleukin 6 levels, and increased circulating erythroid precursors in LPS-exposed pups suggests that these are significant factors associated with potential target organ damage, such as liver hematomas, associated with intrauterine inflammation and preterm birth. The role of macrophages within the fetal leptomeninges is unclear, but they may play an important role in inflammatory-mediated brain damage, and further investigation of their significance and potential as therapeutic targets is warranted.
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