In vivo dysfunction of the term alveolar macrophage after in utero ethanol exposure.
In vivo dysfunction of the term alveolar macrophage after in utero ethanol exposure.
复制标题
子宫内乙醇暴露后术语肺泡巨噬细胞的体内功能障碍。
DOI：
10.1111/j.1530-0277.2006.00306.x
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Gauthier,TheresaW
中科院分区：
文献类型：
--
作者：
Ping,Xiao-Du;Harris,FrankL;Brown,LouAnnS;Gauthier,TheresaW
背景：宫内酒精暴露对新生儿免疫功能的影响仍在研究中。胎儿乙醇（ETOH）暴露会增加发育中肺的氧化应激，部分原因是抗氧化剂谷胱甘肽（GSH）的可用性降低。我们之前已经证明，在子宫内ETOH损害肺泡巨噬细胞的吞噬作用和活力在早产的幼崽，而保持GSH的可用性与S-腺苷-蛋氨酸（SAM）的母亲补充在ETOH摄入改善巨噬细胞的功能和活力。我们假设，在子宫内暴露于ETOH的新生儿肺泡巨噬细胞的功能障碍将持续到足月gestation.Methods：使用胎儿ETOH暴露的豚鼠模型，定时妊娠的豚鼠配对喂养ETOH± GSH前体SAM，饮食持续到自发分娩。用金黄色葡萄球菌体外孵育后，用荧光显微镜观察肺泡巨噬细胞的吞噬和凋亡情况。使用鼻内葡萄球菌的体内模型。结果：子宫内ETOH暴露增加了肺泡巨噬细胞的氧化应激，降低了体外和体内的吞噬功能和生存能力。体内吞噬作用的共聚焦分析表明，ETOH暴露的肺泡巨噬细胞对细菌的内化有明显损害。此外，SAM在母体ETOH摄入防止肺泡巨噬细胞的功能和活力在体外和vivo.Conclusions的损失：在子宫内ETOH暴露损害肺泡巨噬细胞的功能和活力在体外和体内，即使在足月妊娠。ETOH诱导的巨噬细胞功能和活力变化可通过母体SAM补充消除。需要进一步研究以确定ETOH诱导新生儿肺泡巨噬细胞吞噬功能紊乱的机制以及新生儿宫内酒精暴露后免疫功能改变的临床后果。
Background:The effects of in utero alcohol exposure on the immune function of the newborn remain under investigation. Fetal ethanol (ETOH) exposure increases oxidative stress in the developing lung, in part due to decreased availability of the antioxidant glutathione (GSH). We have previously shown that in utero ETOH impairs alveolar macrophage phagocytosis and viability in the premature pup, while maintaining GSH availability with maternal supplementation ofS‐adenosyl‐methionine (SAM) during ETOH ingestion improves macrophage function and viability. We hypothesized that dysfunction of the neonatal alveolar macrophage exposed to ETOH in utero would persist at term gestation.Methods:Using a guinea‐pig model of fetal ETOH exposure, timed‐pregnant guinea‐pigs were pair‐fed ETOH±the GSH precursor SAM and the diet continued until spontaneous delivery. Term alveolar macrophages were evaluated using fluorescent microscopy for phagocytosis and apoptosis after in vitro incubation withStaphalococcus aureus. Using an in vivo model of intranasalStaph. aureusinoculation, the in vivo function of the term alveolar macrophage was also investigated using confocal fluorescent analysis.Results:In utero ETOH exposure increased oxidant stress in the alveolar macrophage and decreased phagocytosis and viability in vitro and in vivo. Confocal analysis of phagocytosis in vivo demonstrated a marked impairment of internalization of the bacteria by the ETOH‐exposed alveolar macrophage. The addition of SAM during maternal ETOH ingestion prevented loss of alveolar macrophage function and viability in vitro and in vivo.Conclusions:In utero ETOH exposure impairs alveolar macrophage function and viability in vitro and in vivo even at term gestation. The ETOH‐induced changes in macrophage function and viability can be ablated with maternal SAM supplementation. Further investigations are required to identify the mechanisms of ETOH‐induced derangement of phagocytosis in the neonatal alveolar macrophage and the clinical ramifications of altered immune function after in utero alcohol exposure for the newborn.