Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein
Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein
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DOI：
10.1126/science.285.5427.595
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发表时间：
1999-07-23
期刊：
影响因子：
56.9
通讯作者：
Pinsky, DJ
中科院分区：
文献类型：
--
作者：
Huang, J;Kim, LJ;Pinsky, DJ
选择素等糖蛋白粘附受体会导致中风中的组织损伤。缺血性神经元强烈表达 C1q，这可能针对它们进行补体介导的攻击或 C1qRp 介导的清除。使用杂合分子同时抑制补体激活和选择素介导的粘附。可溶性补体受体 1 (sCR1) 的胞外结构域被唾液酸路易斯 x 糖基化 (sCR1sLe(x))，以抑制补体激活和内皮-血小板-白细胞相互作用。 sCR1和sCR1sLe(x)共定位于缺血性脑微血管和表达C1q的神经元，抑制中性粒细胞和血小板积累，并减少脑梗塞体积。未修饰的亲本 sCR1 分子的唾液酸路易斯 x 糖基化赋予了额外的好处。
Glycoprotein adhesion receptors such as selectins contribute to tissue injury in stroke. Ischemic neurons strongly expressed C1q, which may target them for complement-mediated attack or C1qRp-mediated clearance. A hybrid molecule was used to simultaneously inhibit both complement activation and selectin-mediated adhesion. The extracellular domain of soluble complement receptor-1 (sCR1) was sialyl Lewis x glycosylated (sCR1sLe(x)) to inhibit complement activation and endothelial-platelet-Leukocyte interactions. sCR1 and sCR1sLe(x) colocalized to ischemic cerebral microvessels and C1q-expressing neurons, inhibited neutrophil and platelet accumulation, and reduced cerebral infarct volumes. Additional benefit was conferred by sialyl Lewis x glycosylation of the unmodified parent sCR1 molecule.