Sialic acid is a critical fetal defense against maternal complement attack
Sialic acid is a critical fetal defense against maternal complement attack
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DOI：
10.1172/jci99945
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发表时间：
2019-01-02
影响因子：
15.9
通讯作者：
Weinhold, Birgit
中科院分区：
文献类型：
--
作者：
Abeln, Markus;Albers, Iris;Weinhold, Birgit
带负电荷的糖唾液酸（Sia）占据细胞表面聚糖主体的最外位置。由于Sia激活酶CMP-唾液酸合酶（CMAS）的基因消除导致缺乏唾液酸化聚糖，导致小鼠在交配后第9.5天左右（E9.5）胚胎死亡。发育失败是由Cmas（-/-）植入物中滋养层细胞上的补体激活引起的，并伴有母体中性粒细胞在胎儿-母体界面的浸润、宫内生长受限、胎盘发育受损和赖歇特膜增厚。这种表型与补体受体1相关蛋白Y（Crry）耗竭具有共同特征，在E8.5 Cmas（-/-）小鼠中注射眼镜蛇毒因子后得到拯救，导致母体补体成分C3耗竭。在这里，我们表明，Sia是胚胎早期发育的关键，但对怀孕期间胎儿-母体免疫稳态至关重要，即，用于保护同种异体移植物免受母体先天免疫系统的攻击。最后，缺乏细胞表面唾液酸化的胚胎由于胎盘形成不足而遭受营养不良作为次要影响。
The negatively charged sugar sialic acid (Sia) occupies the outermost position in the bulk of cell surface glycans. Lack of sialylated glycans due to genetic ablation of the Sia-activating enzyme CMP-sialic acid synthase (CMAS) resulted in embryonic lethality around day 9.5 post coitum (E9.5) in mice. Developmental failure was caused by complement activation on trophoblasts in Cmas(-/-) implants and was accompanied by infiltration of maternal neutrophils at the fetal-maternal interface, intrauterine growth restriction, impaired placental development, and a thickened Reichert's membrane. This phenotype, which shared features with complement receptor 1-related protein Y (Crry) depletion, was rescued in E8.5 Cmas(-/-) mice upon injection of cobra venom factor, resulting in exhaustion of the maternal complement component C3. Here we show that Sia is dispensable for early development of the embryo proper but pivotal for fetal-maternal immune homeostasis during pregnancy, i.e., for protecting the allograft implant against attack by the maternal innate immune system. Finally, embryos devoid of cell surface sialylation suffered from malnutrition due to inadequate placentation as a secondary effect.