Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein

被引：281
作者：
Huang, J
Kim, LJ
Mealey, R
Marsh, HC
Zhang, Y
Tenner, AJ
Connolly, ES
Pinsky, DJ
机构：
[1] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA
[2] Avant Immunotherapeut Inc, Needham, MA 02494 USA
[3] Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA
来源：
SCIENCE | 1999年 / 285卷 / 5427期
关键词：
D O I：
10.1126/science.285.5427.595
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
引用
收藏
页码：595 / 599
页数：5
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